Transcriptional regulation

819:(TADs) containing dozens of genes regulated by hundreds of enhancers distributed within large genomic regions containing only non-coding sequences. The function of TADs is to regroup enhancers and promoters interacting together within a single large functional domain instead of having them spread in different TADs. However, studies of mouse development point out that two adjacent TADs may regulate the same gene cluster. The most relevant study on limb evolution shows that the TAD at the 5’ of the HoxD gene cluster in tetrapod genomes drives its expression in the distal limb bud embryos, giving rise to the hand, while the one located at 3’ side does it in the proximal limb bud, giving rise to the arm. Still, it is not known whether TADs are an adaptive strategy to enhance regulatory interactions or an effect of the constrains on these same interactions. TAD boundaries are often composed by housekeeping genes, tRNAs, other highly expressed sequences and Short Interspersed Elements (SINE). While these genes may take advantage of their border position to be ubiquitously expressed, they are not directly linked with TAD edge formation. The specific molecules identified at boundaries of TADs are called insulators or architectural proteins because they not only block enhancer leaky expression but also ensure an accurate compartmentalization of cis-regulatory inputs to the targeted promoter. These 610:. While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions. It may also happen that a repressor may function by allosteric competition against a determined activator to repress gene expression: overlapping DNA-binding motifs for both activators and repressors induce a physical competition to occupy the site of binding. If the repressor has a higher affinity for its motif than the activator, transcription would be effectively blocked in the presence of the repressor. Tight regulatory control is achieved by the highly dynamic nature of transcription factors. Again, many different mechanisms exist to control whether a transcription factor is active. These mechanisms include control over protein localization or control over whether the protein can bind DNA. An example of this is the protein 353:

largely due to the compaction of the eukaryotic genome by winding DNA around histones to form higher order structures. This compaction makes the gene promoter inaccessible without the assistance of other factors in the nucleus, and thus chromatin structure is a common site of regulation. Similar to the sigma factors in prokaryotes, the general transcription factors (GTFs) are a set of factors in eukaryotes that are required for all transcription events. These factors are responsible for stabilizing binding interactions and opening the DNA helix to allow the RNA polymerase to access the template, but generally lack specificity for different promoter sites. A large part of gene regulation occurs through transcription factors that either recruit or inhibit the binding of the general transcription machinery and/or the polymerase. This can be accomplished through close interactions with core promoter elements, or through the long distance

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the locus. Through DNA looping, active enhancers contact the promoter dependently of the core DNA binding motif promoter specificity. Promoter-enhancer dichotomy provides the basis for the functional interaction between transcription factors and transcriptional core machinery to trigger RNA Pol II escape from the promoter. Whereas one could think that there is a 1:1 enhancer-promoter ratio, studies of the human genome predict that an active promoter interacts with 4 to 5 enhancers. Similarly, enhancers can regulate more than one gene without linkage restriction and are said to “skip” neighboring genes to regulate more distant ones. Even though infrequent, transcriptional regulation can involve elements located in a chromosome different from one where the promoter resides. Proximal enhancers or promoters of neighboring genes can serve as platforms to recruit more distal elements.

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architectural proteins are either of high occupancy and at around a megabase of each other or of low occupancy and inside TADs. High occupancy sites are usually conserved and static while intra-TADs sites are dynamic according to the state of the cell therefore TADs themselves are compartmentalized in subdomains that can be called subTADs from few kb up to a TAD long (19). When architectural binding sites are at less than 100 kb from each other, Mediator proteins are the architectural proteins cooperate with cohesin. For subTADs larger than 100 kb and TAD boundaries, CTCF is the typical insulator found to interact with cohesion.

798:), with one member of the dimer anchored to its binding motif on the enhancer and the other member anchored to its binding motif on the promoter (represented by the red zigzags in the illustration). Several cell function specific transcription factor proteins (in 2018 Lambert et al. indicated there were about 1,600 transcription factors in a human cell) generally bind to specific motifs on an enhancer and a small combination of these enhancer-bound transcription factors, when brought close to a promoter by a DNA loop, govern the level of transcription of the target gene. 282: 718: 815:

evidence that active chromatin regions are “compacted” in nuclear domains or bodies where transcriptional regulation is enhanced. The configuration of the genome is essential for enhancer-promoter proximity. Cell-fate decisions are mediated upon highly dynamic genomic reorganizations at interphase to modularly switch on or off entire gene regulatory networks through short to long range chromatin rearrangements. Related studies demonstrate that metazoan genomes are partitioned in structural and functional units around a megabase long called

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increase or decrease transcription. Repressors often physically occupy the promoter location, occluding RNA polymerase from binding. Alternatively a repressor and polymerase may bind to the DNA at the same time with a physical interaction between the repressor preventing the opening of the DNA for access to the minus strand for transcription. This strategy of control is distinct from eukaryotic transcription, whose basal state is to be off and where co-factors required for transcription initiation are highly gene dependent.

179: 241: 492:. These MBD proteins have both a methyl-CpG-binding domain as well as a transcription repression domain. They bind to methylated DNA and guide or direct protein complexes with chromatin remodeling and/or histone modifying activity to methylated CpG islands. MBD proteins generally repress local chromatin such as by catalyzing the introduction of repressive histone marks, or creating an overall repressive chromatin environment through nucleosome remodeling and chromatin reorganization. 373:, which has consequences for the physical accessibility of parts of the genome at any given time. Significant portions are silenced through histone modifications, and thus are inaccessible to the polymerases or their cofactors. The highest level of transcription regulation occurs through the rearrangement of histones in order to expose or sequester genes, because these processes have the ability to render entire regions of a chromosome inaccessible such as what occurs in imprinting. 573:

activate and/or repress wide repertoires of downstream target genes. The fact that these transcription factors work in a combinatorial fashion means that only a small subset of an organism's genome encodes transcription factors. Transcription factors function through a wide variety of mechanisms. In one mechanism, CpG methylation influences binding of most transcription factors to DNA—in some cases negatively and in others positively. In addition, often they are at the end of a

392:, among others. These enzymes can add or remove covalent modifications such as methyl groups, acetyl groups, phosphates, and ubiquitin. Histone modifications serve to recruit other proteins which can either increase the compaction of the chromatin and sequester promoter elements, or to increase the spacing between histones and allow the association of transcription factors or polymerase on open DNA. For example, H3K27 trimethylation by the 409: 150:. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the 650: 806:

may activate it and that activated transcription factor may then activate the enhancer to which it is bound (see small red star representing phosphorylation of a transcription factor bound to an enhancer in the illustration). An activated enhancer begins transcription of its RNA before activating a promoter to initiate transcription of messenger RNA from its target gene.

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transcription. In a hypothetical example, the factors A and B might regulate a distinct set of genes from the combination of factors A and C. This combinatorial nature extends to complexes of far more than two proteins, and allows a very small subset (less than 10%) of the genome to control the transcriptional program of the entire cell.

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are sequences of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene expression programs, most often by looping through long distances to come in physical proximity with the promoters of their target genes. In a study of brain cortical neurons, 24,937 loops

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are proteins that bind to specific DNA sequences in order to regulate the expression of a given gene. There are approximately 1,400 transcription factors in the human genome and they constitute about 6% of all human protein coding genes. The power of transcription factors resides in their ability to

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The splice isoform DNMT3A2 behaves like the product of a classical immediate-early gene and, for instance, it is robustly and transiently produced after neuronal activation. Where the DNA methyltransferase isoform DNMT3A2 binds and adds methyl groups to cytosines appears to be determined by histone

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transcription factor binding site is frequently located in enhancer or promoter sequences. There are about 12,000 binding sites for EGR1 in the mammalian genome and about half of EGR1 binding sites are located in promoters and half in enhancers. The binding of EGR1 to its target DNA binding site is

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are proteins that bind to specific DNA sequences in order to regulate the expression of a gene. The binding sequence for a transcription factor in DNA is usually about 10 or 11 nucleotides long. As summarized in 2009, Vaquerizas et al. indicated there are approximately 1,400 different transcription

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elongation factor), have kinase activity towards other residues on the CTD. These phosphorylation events promote the transcription process and serve as sites of recruitment for mRNA processing machinery. All three of these kinases respond to upstream signals, and failure to phosphorylate the CTD can

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where they can interact with their corresponding enhancers. Other transcription factors are already in the nucleus, and are modified to enable the interaction with partner transcription factors. Some post-translational modifications known to regulate the functional state of transcription factors are

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marker found predominantly within CpG sites. About 28 million CpG dinucleotides occur in the human genome. In most tissues of mammals, on average, 70% to 80% of CpG cytosines are methylated (forming 5-methylCpG or 5-mCpG). Methylated cytosines within 5’cytosine-guanine 3’ sequences often occur in

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Once a polymerase is successfully bound to a DNA template, it often requires the assistance of other proteins in order to leave the stable promoter complex and begin elongating the nascent RNA strand. This process is called promoter escape, and is another step at which regulatory elements can act to

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In the absence of other regulatory elements, the default state of a bacterial transcript is to be in the “on” configuration, resulting in the production of some amount of transcript. This means that transcriptional regulation in the form of protein repressors and positive control elements can either

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The transcription of a basic bacterial gene is dependent on the strength of its promoter and the presence of activators or repressors. In the absence of other regulatory elements, a promoter's sequence-based affinity for RNA polymerases varies, which results in the production of different amounts of

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sequences containing multiple activator and repressor binding sites. Enhancers range from 200 bp to 1 kb in length and can be either proximal, 5’ upstream to the promoter or within the first intron of the regulated gene, or distal, in introns of neighboring genes or intergenic regions far away from

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are specialized bacterial proteins that bind to RNA polymerases and orchestrate transcription initiation. Sigma factors act as mediators of sequence-specific transcription, such that a single sigma factor can be used for transcription of all housekeeping genes or a suite of genes the cell wishes to

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can assemble. This complex is relatively stable, and can undergo multiple rounds of transcription initiation. After the binding of TFIIB and TFIID, Pol II the rest of the GTFs can assemble. This assembly is marked by the post-translational modification (typically phosphorylation) of the C-terminal

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Enhancers, when active, are generally transcribed from both strands of DNA with RNA polymerases acting in two different directions, producing two eRNAs as illustrated in the Figure. An inactive enhancer may be bound by an inactive transcription factor. Phosphorylation of the transcription factor

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the methylated CpG islands at those promoters. Upon demethylation, these promoters can then initiate transcription of their target genes. Hundreds of genes in neurons are differentially expressed after neuron activation through EGR1 recruitment of TET1 to methylated regulatory sequences in their

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Transcriptional initiation, termination and regulation are mediated by “DNA looping” which brings together promoters, enhancers, transcription factors and RNA processing factors to accurately regulate gene expression. Chromosome conformation capture (3C) and more recently Hi-C techniques provided

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gene into protein at one hour after stimulation is drastically elevated. Expression of EGR1 transcription factor proteins, in various types of cells, can be stimulated by growth factors, neurotransmitters, hormones, stress and injury. In the brain, when neurons are activated, EGR1 proteins are

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to bind to the mal promoter (#3). Transcription of malE, malF, and malG genes then proceeds (#4) as maltose activator protein and RNA polymerase moves down the DNA. malE encodes for maltose-binding periplasmic protein and helps maltose transport across the cell membrane. malF encodes for maltose

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shown by a small red star on a transcription factor on the enhancer) the enhancer is activated and can now activate its target promoter. The active enhancer is transcribed on each strand of DNA in opposite directions by bound RNAP IIs. Mediator (a complex consisting of about 26 proteins in an

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are DNA-binding proteins like CTCF and TFIIIC that help recruiting structural partners such as cohesins and condensins. The localization and binding of architectural proteins to their corresponding binding sites is regulated by post-translational modifications. DNA binding motifs recognized by

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While in prokaryotic systems the basal transcription state can be thought of as nonrestrictive (that is, “on” in the absence of modifying factors), eukaryotes have a restrictive basal state which requires the recruitment of other factors in order to generate RNA transcripts. This difference is

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have very different strategies of accomplishing control over transcription, but some important features remain conserved between the two. Most importantly is the idea of combinatorial control, which is that any given gene is likely controlled by a specific combination of factors to control

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factors encoded in the human genome by genes that constitute about 6% of all human protein encoding genes. About 94% of transcription factor binding sites (TFBSs) that are associated with signal-responsive genes occur in enhancers while only about 6% of such TFBSs occur in promoters.

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were found, bringing enhancers to promoters. Multiple enhancers, each often at tens or hundred of thousands of nucleotides distant from their target genes, loop to their target gene promoters and coordinate with each other to control expression of their common target gene.

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In addition to processes that regulate transcription at the stage of initiation, mRNA synthesis is also controlled by the rate of transcription elongation. RNA polymerase pauses occur frequently and are regulated by transcription factors, such as NusG and NusA,

331:. Each polymerase has specific targets and activities, and is regulated by independent mechanisms. There are a number of additional mechanisms through which polymerase activity can be controlled. These mechanisms can be generally grouped into three main areas: 762:

that are located in DNA regions distant from the promoters of genes can have very large effects on gene expression, with some genes undergoing up to 100-fold increased expression due to such a cis-regulatory sequence. These cis-regulatory sequences include

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or passenger mutations. However, transcriptional silencing may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation (see

802:(a complex usually consisting of about 26 proteins in an interacting structure) communicates regulatory signals from enhancer DNA-bound transcription factors directly to the RNA polymerase II (RNAP II) enzyme bound to the promoter. 195:

Much of the early understanding of transcription came from bacteria, although the extent and complexity of transcriptional regulation is greater in eukaryotes. Bacterial transcription is governed by three main sequence elements:

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Dukatz M, Holzer K, Choudalakis M, Emperle M, Lungu C, Bashtrykov P, Jeltsch A (December 2019). "H3K36me2/3 Binding and DNA Binding of the DNA Methyltransferase DNMT3A PWWP Domain Both Contribute to its Chromatin Interaction".

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in the cytosol and is only translocated into the nucleus upon cellular stress such as heat shock. Thus the genes under the control of this transcription factor will remain untranscribed unless the cell is subjected to stress.

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The schematic illustration in this section shows an enhancer looping around to come into close physical proximity with the promoter of a target gene. The loop is stabilized by a dimer of a connector protein (e.g. dimer of

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of the maltose genes will occur, and there is no maltose to bind to the maltose activator protein. This prevents the activator protein from binding to the activator binding site on the gene, which in turn prevents

538:(DNMT1, DNMT3A, and DNMT3B) catalyze the addition of methyl groups to cytosines in DNA. While DNMT1 is a “maintenance” methyltransferase, DNMT3A and DNMT3B can carry out new methylations. There are also two 361:

accelerate or slow the transcription process. Similarly, protein and nucleic acid factors can associate with the elongation complex and modulate the rate at which the polymerase moves along the DNA template.

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While these means of transcriptional regulation also exist in eukaryotes, the transcriptional landscape is significantly more complicated both by the number of proteins involved as well as by the presence of

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of the gene. The loop is stabilized by one architectural protein anchored to the enhancer and one anchored to the promoter and these proteins are joined to form a dimer (red zigzags). Specific regulatory

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Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schübeler D, Vinson C, Taipale J (May 2017).

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Productive elongation of the RNA transcript. Once polymerase is bound to a promoter, it requires another set of factors to allow it to escape the promoter complex and begin successfully transcribing RNA.

885:, the helicase that remains associated with Pol II throughout transcription, also contains a subunit with kinase activity which will phosphorylate the serines 5 in the heptad sequence. Similarly, both 253:

transport system permease protein and helps translocate maltose across the cell membrane. malG encodes for transport system protein and also helps translocate maltose across the cell membrane.

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upstream of the transcription start site. The more nucleotides of a promoter that agree with the consensus sequence, the stronger the affinity of the promoter for RNA Polymerase likely is.

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pathway that functions to change something about the factor, like its subcellular localization or its activity. Post-translational modifications to transcription factors located in the

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sequences have a CpG island. CpG islands constitute regulatory sequences, since if CpG islands are methylated in the promoter of a gene this can reduce or silence gene transcription.

420:. The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a 319:

The added complexity of generating a eukaryotic cell carries with it an increase in the complexity of transcriptional regulation. Eukaryotes have three RNA polymerases, known as

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is present in E. coli, it binds to the maltose activator protein (#1), which promotes maltose activator protein binding to the activator binding site (#2). This allows the

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bind to DNA sequence motifs on the enhancer. General transcription factors bind to the promoter. When a transcription factor is activated by a signal (here indicated as

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products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in

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Termination of the polymerase. A number of factors which have been found to control how and when termination occurs, which will dictate the fate of the RNA transcript.

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In eukaryotes, genomic DNA is highly compacted in order to be able to fit it into the nucleus. This is accomplished by winding the DNA around protein octamers called

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Whiteside ST, Goodbourn S (April 1993). "Signal transduction and nuclear targeting: regulation of transcription factor activity by subcellular localisation".

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can catalyse demethylation of 5-methylcytosine. When EGR1 transcription factors bring TET1 enzymes to EGR1 binding sites in promoters, the TET enzymes can

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Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L, Zhu J, Chen J, Morozov A, Pickrell AM, Theus MH, Xie H (August 2019).

856:(mRNA) within the cell. Particularly for Pol II, much of the regulatory checkpoints in the transcription process occur in the assembly and escape of the 1810:

Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (April 2009). "A census of human transcription factors: function, expression and evolution".

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On the other hand, neural activation causes degradation of DNMT3A1 accompanied by reduced methylation of at least one evaluated targeted promoter.

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de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, Koseki H, Brockdorff N (November 2004).

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Bayraktar G, Yuanxiang P, Confettura AD, Gomes GM, Raza SA, Stork O, Tajima S, Suetake I, Karpova A, Yildirim F, Kreutz MR (November 2020).

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Oliveira AM, Hemstedt TJ, Bading H (July 2012). "Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities".

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Control over polymerase access to the gene. This is perhaps the broadest of the three control mechanisms. This includes the functions of

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Tessitore A, Cicciarelli G, Del Vecchio F, Gaggiano A, Verzella D, Fischietti M, Vecchiotti D, Capece D, Zazzeroni F, Alesse E (2014).

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Up-regulated expression of genes in mammals can be initiated when signals are transmitted to the promoters associated with the genes.

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and other proteins working in concert to finely tune the amount of RNA being produced through a variety of mechanisms. Bacteria and

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All three of these systems work in concert to integrate signals from the cell and change the transcriptional program accordingly.

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While only small amounts of EGR1 transcription factor protein are detectable in cells that are un-stimulated, translation of the

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Wang H, Maurano MT, Qu H, Varley KE, Gertz J, Pauli F, Lee K, Canfield T, Weaver M, Sandstrom R, Thurman RE, Kaul R, Myers RM,

3510:"Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation" 1095:

Busby S, Ebright RH (December 1994). "Promoter structure, promoter recognition, and transcription activation in prokaryotes".

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causes chromosomal compaction and gene silencing. These histone modifications may be created by the cell, or inherited in an

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interacting structure) communicates regulatory signals from the enhancer DNA-bound transcription factors to the promoter.

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Napolitano G, Lania L, Majello B (May 2014). "RNA polymerase II CTD modifications: how many tales from a single tail".

3435: 270: 155: 3939: 987: 704: 1548:"Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation" 182:

The maltose operon is an example of a positive control of transcription. When maltose is not present in E. coli, no

74:– a substance, such as a protein, that contributes to the cause of a specific biochemical reaction or bodily process 954: 432:

is controlled by methylation of cytosines within CpG dinucleotides (where 5’ cytosine is followed by 3’ guanine or

929: 913: 4093: 4037: 3559:"A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters" 2977:"Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems" 2879:"The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription" 1189:"malG - Maltose transport system permease protein MalG - Escherichia coli (strain K12) - malG gene & protein" 1164:"malF - Maltose transport system permease protein MalF - Escherichia coli (strain K12) - malF gene & protein" 505:

protein is a particular transcription factor that is important for regulation of methylation of CpG islands. An

1139:"malE - Maltose-binding periplasmic protein precursor - Escherichia coli (strain K12) - malE gene & protein" 4032: 2649:

Spitz F, Furlong EE (September 2012). "Transcription factors: from enhancer binding to developmental control".

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domain (CTD) of Pol II through a number of kinases. The CTD is a large, unstructured domain extending from the

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transcript. The variable affinity of RNA polymerase for different promoter sequences is related to regions of

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Gruber TM, Gross CA (2003). "Multiple sigma subunits and the partitioning of bacterial transcription space".

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may occur more frequently by over-expressed microRNA-182 than by hypermethylation of the BRCA1 promoter (see

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Schoenfelder S, Fraser P (August 2019). "Long-range enhancer-promoter contacts in gene expression control".

3856: 2928:"MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300" 2551:"Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression" 2271:"Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus" 535: 381: 3324:

Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR, Bell JS, et al. (June 2013).

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Carullo NV, Phillips Iii RA, Simon RC, Soto SA, Hinds JE, Salisbury AJ, et al. (September 2020).

2035:"Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression?" 1982:

Kubosaki A, Tomaru Y, Tagami M, Arner E, Miura H, Suzuki T, Suzuki M, Suzuki H, Hayashizaki Y (2009).

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to the tails of the core histones. A wide variety of modifications can be made by enzymes such as the

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recognize repressor proteins that bind to a stretch of DNA and inhibit the transcription of the gene.

3387: 3222:"Conservation and divergence of regulatory strategies at Hox Loci and the origin of tetrapod digits" 2877:

Mikhaylichenko O, Bondarenko V, Harnett D, Schor IE, Males M, Viales RR, Furlong EE (January 2018).

2178:"Isoform-specific localization of DNMT3A regulates DNA methylation fidelity at bivalent CpG islands" 90:– specialized bacterial co-factors that complex with RNA Polymerase and encode sequence specificity 4174: 4115: 3903: 3816: 3785: 3768:

Plant Transcription Factor Database and Plant Transcriptional Regulation Data and Analysis Platform

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The regulation of transcription is a vital process in all living organisms. It is orchestrated by

143: 51: 3075:"Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data" 4076: 3893: 3878: 3272: 1636:

Jabbari K, Bernardi G (May 2004). "Cytosine methylation and CpG, TpG (CpA) and TpA frequencies".

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and other proteins for the successful initiation of transcription directly upstream of the gene.

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the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA

4081: 4006: 3898: 3382: 1924:"EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity" 799: 759: 628: 106: 94: 2125:

Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A (August 2010).

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and tethering elements. Among this constellation of sequences, enhancers and their associated

3996: 3981: 3861: 3326:"Architectural protein subclasses shape 3D organization of genomes during lineage commitment" 3026:"Understanding the regulatory and transcriptional complexity of the genome through structure" 2738:

Weintraub AS, Li CH, Zamudio AV, Sigova AA, Hannett NM, Day DS, et al. (December 2017).

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remodeling enzymes, transcription factors, enhancers and repressors, and many other complexes

162: 2321:"Impact of cytosine methylation on DNA binding specificities of human transcription factors" 2127:"The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation" 1003:

JACOB F, MONOD J (June 1961). "Genetic regulatory mechanisms in the synthesis of proteins".

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Thomas MC, Chiang CM (2006). "The general transcription machinery and general cofactors".

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The methylation of promoters is also altered in response to signals. The three mammalian

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Beagan JA, Pastuzyn ED, Fernandez LR, Guo MH, Feng K, Titus KR, et al. (June 2020).

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Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, et al. (February 2018).

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Positive control elements that bind to DNA and incite higher levels of transcription.

123: 4148: 3494: 3412: 2111: 1673:"Pervasive and CpG-dependent promoter-like characteristics of transcribed enhancers" 1483: 1124: 1032: 397: 3737: 3727: 3686: 3678: 3629: 3588: 3578: 3529: 3521: 3474: 3392: 3345: 3337: 3296: 3288: 3243: 3233: 3192: 3184: 3143: 3135: 3094: 3086: 3045: 3037: 2996: 2988: 2947: 2939: 2898: 2890: 2849: 2841: 2800: 2759: 2751: 2704: 2658: 2621: 2611: 2570: 2562: 2518: 2510: 2469: 2461: 2420: 2381: 2340: 2332: 2290: 2282: 2235: 2197: 2189: 2148: 2138: 2091: 2054: 2046: 2005: 1995: 1951: 1943: 1887: 1877: 1858:"Positional specificity of different transcription factor classes within enhancers" 1839: 1819: 1779: 1733: 1692: 1684: 1645: 1608: 1600: 1559: 1518: 1510: 1461: 1420: 1410: 1369: 1361: 1320: 1310: 1271: 1234: 1226: 1104: 1067: 1059: 1012: 841: 437: 320: 2926:

Li QJ, Yang SH, Maeda Y, Sladek FM, Sharrocks AD, Martins-Green M (January 2003).

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Manzo M, Wirz J, Ambrosi C, Villaseñor R, Roschitzki B, Baubec T (December 2017).

4125: 3962: 3808: 3657:

Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (2013).

3238: 1564: 1547: 1514: 1063: 925: 750: 724:. An active enhancer regulatory sequence of DNA is enabled to interact with the 587: 542: 147: 1450:"Fundamentally different logic of gene regulation in eukaryotes and prokaryotes" 881:

subunit of Pol II, and consists of many repeats of the heptad sequence YSPTSPS.

3952: 3924: 3341: 3173:"Genome organization and long-range regulation of gene expression by enhancers" 2805: 2788: 2755: 1947: 1862:

Proceedings of the National Academy of Sciences of the United States of America

1649: 1365: 1296: 917: 632: 489: 458: 249: 204: 188: 64: 3396: 3188: 3139: 2708: 2616: 2566: 2514: 2465: 2286: 2239: 1856:

Grossman SR, Engreitz J, Ray JP, Nguyen TH, Hacohen N, Lander ES (July 2018).

1315: 1230: 4168: 4153: 3840: 2050: 2000: 853: 833: 733: 677: 3682: 3583: 2499:"In search of the determinants of enhancer-promoter interaction specificity" 2336: 2193: 2143: 1882: 1589:"DNA methylation in human epigenomes depends on local topology of CpG sites" 4027: 3957: 3826: 3751: 3700: 3643: 3602: 3543: 3486: 3404: 3359: 3310: 3257: 3206: 3157: 3124:"Architectural proteins: regulators of 3D genome organization in cell fate" 3108: 3059: 3010: 2961: 2943: 2912: 2894: 2863: 2814: 2773: 2716: 2670: 2635: 2584: 2532: 2483: 2434: 2354: 2304: 2247: 2211: 2162: 2103: 2068: 2019: 1965: 1901: 1831: 1793: 1747: 1706: 1657: 1622: 1573: 1532: 1475: 1434: 1383: 1334: 1283: 1248: 1024: 837: 582: 302: 294: 261: 86: 3732: 3292: 3041: 2992: 2393: 2385: 1688: 1116: 1081: 1048:"Positive control of enzyme synthesis by gene C in the L-arabinose system" 336: 4130: 4059: 1604: 1188: 1163: 1138: 595: 591: 523: 519: 453: 441: 2600:"The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1" 4088: 3713: 3634: 3617: 2425: 2408: 1738: 1721: 166: 3478: 3323: 1784: 1767: 1415: 472:

DNA methylation regulates gene transcription through interaction with

3767: 2496: 1809: 928:

the gene becomes silenced. Colorectal cancers typically have 3 to 6

599: 433: 312: 298: 286: 3656: 3090: 2876: 2845: 2662: 2095: 1823: 860:. A gene-specific combination of transcription factors will recruit 827: 4108: 4098: 4022: 3277:"Widespread plasticity in CTCF occupancy linked to DNA methylation" 2597: 1297:

Kang, J.; Mishanina, T. V.; Landick, R. & Darst, S. A. (2019).

921: 449: 417: 370: 226: 191:

from binding to the maltose promoter. No transcription takes place.

127: 82:– a region of DNA that initiates transcription of a particular gene 3777: 2497:

van Arensbergen J, van Steensel B, Bussemaker HJ (November 2014).

408: 3844: 2268: 941:). Transcriptional repression in cancer can also occur by other 578: 421: 245: 222: 3220:

Woltering JM, Noordermeer D, Leleu M, Duboule D (January 2014).

3219: 2450:"Transcriptional enhancers in animal development and evolution" 1670: 894: 878: 602:. Transcription factors can be divided in two main categories: 413: 210: 2224: 1768:"Methyl-CpG-binding domain proteins: readers of the epigenome" 559: 488:. These MBD proteins bind most strongly to highly methylated 3866: 2830:"The Mediator complex: a central integrator of transcription" 1399:"Rebuilding the bridge between transcription and translation" 950: 889:(a subunit of the massive multiprotein Mediator complex) and 615: 477: 290: 265:

express in response to some external stimuli such as stress.

3773:

MIT : Activating a new understanding of gene regulation

2974: 2598:

Verheul TC, van Hijfte L, Perenthaler E, Barakat TS (2020).

2124: 1671:

Steinhaus R, Gonzalez T, Seelow D, Robinson PN (June 2020).

1215:"Transcriptional repression: conserved and evolved features" 890: 886: 791: 729: 611: 506: 502: 481: 393: 151: 2740:"YY1 Is a Structural Regulator of Enhancer-Promoter Loops" 2548: 2175: 1586: 1545: 779:

have a leading role in the regulation of gene expression.

722:

Enhance function in regulation of transcription in mammals

549:

gene: DNA methyltransferase proteins DNMT3A1 and DNMT3A2.

305:, wherein the lighter staining regions are generally more 3836: 2786: 2317: 1981: 1855: 1499:"Modification of enhancer chromatin: what, how, and why?" 795: 639: 518:

up-regulated and they bind to (recruit) the pre-existing

445: 139: 135: 134:

is the means by which a cell regulates the conversion of

60: 56: 2737: 1587:

Lövkvist C, Dodd IB, Sneppen K, Haerter JO (June 2016).

3716:"MicroRNAs in the DNA Damage/Repair Network and Cancer" 872:, creating a stable complex onto which the rest of the 403: 3464: 3072: 2081: 732:

by formation of a chromosome loop. This can initiate

1045: 955:

Low expression of BRCA1 in breast and ovarian cancers

868:

to the core promoter, followed by the association of

110:– a protein that works with transcription factors to 98:– a protein that works with transcription factors to 3430:(4th ed.). Hoboken, NJ: John Wiley & Sons. 1347: 1212: 1046:

Englesberg E, Irr J, Power J, Lee N (October 1965).

3270: 1765: 1299:"Mechanisms of Transcriptional Pausing in Bacteria" 1213:Payankaulam S, Li LM, Arnosti DN (September 2010). 949:. In breast cancer, transcriptional repression of 465:sequences have a CpG island while only about 6% of 3556: 2694: 2406: 2375: 364: 3507: 2925: 828:Of the pre-initiation complex and promoter escape 309:active, whereas darker regions are more inactive. 4166: 3618:"DNA methylation patterns and epigenetic memory" 3121: 3073:Dekker J, Marti-Renom MA, Mirny LA (June 2013). 1722:"DNA methylation patterns and epigenetic memory" 1396: 1390: 924:. When many of a gene's promoter CpG sites are 522:enzymes which are highly expressed in neurons. 510:insensitive to cytosine methylation in the DNA. 3508:Chapman RD, Conrad M, Eick D (September 2005). 2690: 2688: 2032: 1851: 1849: 1635: 898:lead to a stalled polymerase at the promoter. 852:(Pol II) is responsible for the production of 3793: 3023: 1921: 1805: 1803: 3707: 3650: 3550: 3501: 3458: 3450:: CS1 maint: multiple names: authors list ( 3372: 3366: 3317: 3264: 3213: 3170: 3164: 3115: 3066: 3017: 2968: 2919: 2870: 2827: 2780: 2731: 2685: 2648: 2642: 2591: 2490: 2441: 2400: 2311: 2262: 2218: 2169: 2118: 2075: 2026: 1846: 1766:Du Q, Luu PL, Stirzaker C, Clark SJ (2015). 1713: 1664: 1629: 1580: 1539: 1490: 1441: 1094: 2604:Frontiers in Cell and Developmental Biology 2369: 1977: 1975: 1496: 1261: 1255: 1206: 996: 560:Through transcription factors and enhancers 3948:Precursor mRNA (pre-mRNA / hnRNA) 3800: 3786: 1800: 1088: 1039: 1002: 945:mechanisms, such as altered expression of 840:involved in translation are controlled by 3741: 3731: 3690: 3633: 3592: 3582: 3533: 3386: 3349: 3300: 3247: 3237: 3196: 3147: 3122:Gómez-Díaz E, Corces VG (November 2014). 3098: 3049: 3000: 2951: 2902: 2853: 2821: 2804: 2763: 2625: 2615: 2574: 2544: 2542: 2522: 2473: 2424: 2407:Vihervaara A, Sistonen L (January 2014). 2344: 2294: 2201: 2152: 2142: 2058: 2009: 1999: 1955: 1891: 1881: 1783: 1737: 1696: 1612: 1563: 1522: 1465: 1424: 1414: 1373: 1341: 1324: 1314: 1238: 1071: 705:Learn how and when to remove this message 428:Transcription regulation at about 60% of 27:Control of DNA to RNA conversion in cells 1972: 1290: 716: 564: 407: 376:Histone rearrangement is facilitated by 280: 239: 177: 1917: 1915: 1913: 1911: 973: 971: 969: 809: 740:(RNAP II) bound to the promoter at the 14: 4167: 3557:Saxonov S, Berg P, Brutlag DL (2006). 2834:Nature Reviews. Molecular Cell Biology 2539: 2447: 1447: 1276:10.1146/annurev.micro.57.030502.090913 728:DNA regulatory sequence of its target 640:Enhancer activation and implementation 3968:Histone acetylation and deacetylation 3781: 3426:Voet, Donald Voet, Judith G. (2011). 2033:Bayraktar G, Kreutz MR (April 2018). 1761: 1759: 1757: 939:regulation of transcription in cancer 912:In vertebrates, the majority of gene 908:Regulation of transcription in cancer 581:can cause them to translocate to the 412:DNA methylation is the addition of a 4033:Ribosome-nascent chain complex (RNC) 3615: 3609: 3425: 1908: 1719: 1348:Zhang, J. & Landick, R. (2016). 980:Brock Biology of Microorganisms, 15e 966: 874:General Transcription Factors (GTFs) 643: 474:methyl binding domain (MBD) proteins 404:At the level of cytosine methylation 3807: 3024:Mercer TR, Mattick JS (July 2013). 2828:Allen BL, Taatjes DJ (March 2015). 977: 24: 1754: 553:post translational modifications. 301:, which is a method that includes 271:transcription-translation coupling 203:are elements of DNA that may bind 156:evolutionary developmental biology 25: 4186: 3761: 2789:"The Human Transcription Factors" 416:group to the DNA that happens at 386:histone methyltransferases (HMTs) 382:histone acetyltransferases (HATs) 33:Transcription regulation glossary 3526:10.1128/MCB.25.17.7665-7674.2005 3171:Smallwood A, Ren B (June 2013). 1497:Calo E, Wysocka J (March 2013). 648: 378:post-translational modifications 276: 273:, and mRNA secondary structure. 4038:Post-translational modification 3419: 817:Topological association domains 629:cis-regulatory modules/elements 365:At the level of chromatin state 1181: 1156: 1131: 225:and the packaging of DNA into 173: 114:the rate of gene transcription 102:the rate of gene transcription 13: 1: 3375:Crit. Rev. Biochem. Mol. Biol 1467:10.1016/S0092-8674(00)80599-1 1017:10.1016/s0022-2836(61)80072-7 960: 777:transcription factor proteins 293:, showing an overview of the 3563:Proc. Natl. Acad. Sci. U.S.A 3239:10.1371/journal.pbio.1001773 1565:10.1016/j.devcel.2004.10.005 1515:10.1016/j.molcel.2013.01.038 1354:Journal of Molecular Biology 1303:Journal of Molecular Biology 1109:10.1016/0092-8674(94)90063-9 1064:10.1128/JB.90.4.946-957.1965 901: 760:Cis-regulatory DNA sequences 622: 390:histone deacetylases (HDACs) 7: 2448:Levine M (September 2010). 2380:. 104 ( Pt 4) (4): 949–55. 668:. The specific problem is: 148:orchestrating gene activity 10: 4191: 3659:"Cancer genome landscapes" 3342:10.1016/j.cell.2013.04.053 2806:10.1016/j.cell.2018.01.029 2756:10.1016/j.cell.2017.11.008 1948:10.1038/s41467-019-11905-3 1650:10.1016/j.gene.2004.02.043 1366:10.1016/j.tibs.2015.12.009 905: 452:(see Figure). 5-mC is an 310: 132:transcriptional regulation 41:transcriptional regulation 4141: 4050: 4015: 3989: 3980: 3938: 3912: 3886: 3877: 3815: 3397:10.1080/10409230600648736 3189:10.1016/j.ceb.2013.02.005 3140:10.1016/j.tcb.2014.08.003 2709:10.1038/s41576-019-0128-0 2617:10.3389/fcell.2020.592164 2567:10.1038/s41593-020-0634-6 2515:10.1016/j.tcb.2014.07.004 2466:10.1016/j.cub.2010.06.070 2287:10.1038/s41386-020-0780-2 2240:10.1016/j.jmb.2019.09.006 1397:Artsimovitch, I. (2018). 1316:10.1016/j.jmb.2019.07.017 1231:10.1016/j.cub.2010.06.037 614:, which remains bound to 37: 32: 4099:sequestration (P-bodies) 2697:Nature Reviews. Genetics 2651:Nature Reviews. Genetics 2051:10.1177/1073858417707457 2001:10.1186/gb-2009-10-4-r41 982:. Pearson. p. 178. 742:transcription start site 55:– the process of making 18:Transcription regulation 4077:Gene regulatory network 3683:10.1126/science.1235122 3584:10.1073/pnas.0510310103 2883:Genes & Development 2337:10.1126/science.aaj2239 2275:Neuropsychopharmacology 2194:10.15252/embj.201797038 2144:10.1074/jbc.M109.089433 1883:10.1073/pnas.1804663115 1720:Bird A (January 2002). 932:mutations and 33 to 66 536:DNA methyltransferasess 400:fashion from a parent. 4082:cis-regulatory element 2981:Nucleic Acids Research 2895:10.1101/gad.308619.117 1448:Struhl K (July 1999). 1403:Molecular Microbiology 858:pre-initiation complex 800:Mediator (coactivator) 755: 425: 316: 254: 192: 3293:10.1101/gr.136101.111 3273:Stamatoyannopoulos JA 3177:Curr. Opin. Cell Biol 3042:10.1101/gr.156612.113 2386:10.1242/jcs.104.4.949 747:transcription factors 720: 570:Transcription factors 565:Transcription factors 496:Transcription factors 411: 394:polycomb complex PRC2 311:Further information: 284: 243: 181: 163:transcription factors 4104:alternative splicing 4094:Post-transcriptional 3920:Transcription factor 2944:10.1093/emboj/cdg028 2750:(7): 1573–1588.e28. 1264:Annu. Rev. Microbiol 978:Madigan, Michael T. 810:Regulatory landscape 736:(mRNA) synthesis by 687:improve this section 664:to meet Knowledge's 71:transcription factor 4028:Transfer RNA (tRNA) 3733:10.1155/2014/820248 3675:2013Sci...339.1546V 3575:2006PNAS..103.1412S 2993:10.1093/nar/gkaa671 2555:Nature Neuroscience 1940:2019NatCo..10.3892S 1874:2018PNAS..115E7222G 1868:(30): E7222–E7230. 1689:10.1093/nar/gkaa223 672:Enhancer (genetics) 575:signal transduction 4142:Influential people 4121:Post-translational 3940:Post-transcription 3635:10.1101/gad.947102 3275:(September 2012). 2426:10.1242/jcs.132605 2409:"HSF1 at a glance" 2331:(6337): eaaj2239. 1739:10.1101/gad.947102 1605:10.1093/nar/gkw124 893:(a subunit of the 846:RNA polymerase III 756: 545:produced from the 426: 317: 255: 235:consensus sequence 193: 4162: 4161: 4046: 4045: 3976: 3975: 3852:Special transfers 3669:(6127): 1546–58. 3479:10.1002/jcp.24483 2987:(17): 9550–9570. 2281:(12): 2120–2130. 2234:(24): 5063–5074. 2188:(23): 3421–3434. 1785:10.2217/epi.15.39 1683:(10): 5306–5317. 1677:Nucleic Acids Res 1593:Nucleic Acids Res 1416:10.1111/mmi.13964 1309:(20): 4007–4029. 850:RNA Polymerase II 738:RNA polymerase II 715: 714: 707: 670:Duplication with 666:quality standards 657:This section may 307:transcriptionally 124:molecular biology 120: 119: 16:(Redirected from 4182: 3987: 3986: 3884: 3883: 3802: 3795: 3788: 3779: 3778: 3756: 3755: 3745: 3735: 3711: 3705: 3704: 3694: 3654: 3648: 3647: 3637: 3613: 3607: 3606: 3596: 3586: 3554: 3548: 3547: 3537: 3505: 3499: 3498: 3467:J. Cell. Physiol 3462: 3456: 3455: 3449: 3441: 3423: 3417: 3416: 3390: 3370: 3364: 3363: 3353: 3321: 3315: 3314: 3304: 3268: 3262: 3261: 3251: 3241: 3217: 3211: 3210: 3200: 3168: 3162: 3161: 3151: 3128:Trends Cell Biol 3119: 3113: 3112: 3102: 3070: 3064: 3063: 3053: 3021: 3015: 3014: 3004: 2972: 2966: 2965: 2955: 2932:The EMBO Journal 2923: 2917: 2916: 2906: 2874: 2868: 2867: 2857: 2825: 2819: 2818: 2808: 2784: 2778: 2777: 2767: 2735: 2729: 2728: 2692: 2683: 2682: 2646: 2640: 2639: 2629: 2619: 2595: 2589: 2588: 2578: 2546: 2537: 2536: 2526: 2503:Trends Cell Biol 2494: 2488: 2487: 2477: 2445: 2439: 2438: 2428: 2404: 2398: 2397: 2373: 2367: 2366: 2348: 2315: 2309: 2308: 2298: 2266: 2260: 2259: 2222: 2216: 2215: 2205: 2173: 2167: 2166: 2156: 2146: 2137:(34): 26114–20. 2122: 2116: 2115: 2079: 2073: 2072: 2062: 2030: 2024: 2023: 2013: 2003: 1979: 1970: 1969: 1959: 1919: 1906: 1905: 1895: 1885: 1853: 1844: 1843: 1807: 1798: 1797: 1787: 1763: 1752: 1751: 1741: 1717: 1711: 1710: 1700: 1668: 1662: 1661: 1633: 1627: 1626: 1616: 1584: 1578: 1577: 1567: 1543: 1537: 1536: 1526: 1494: 1488: 1487: 1469: 1445: 1439: 1438: 1428: 1418: 1394: 1388: 1387: 1377: 1345: 1339: 1338: 1328: 1318: 1294: 1288: 1287: 1259: 1253: 1252: 1242: 1210: 1204: 1203: 1201: 1199: 1185: 1179: 1178: 1176: 1174: 1160: 1154: 1153: 1151: 1149: 1135: 1129: 1128: 1092: 1086: 1085: 1075: 1043: 1037: 1036: 1000: 994: 993: 975: 842:RNA polymerase I 710: 703: 699: 696: 690: 681: 652: 651: 644: 543:protein isoforms 461:. About 60% of 438:5-methylcytosine 30: 29: 21: 4190: 4189: 4185: 4184: 4183: 4181: 4180: 4179: 4175:Gene expression 4165: 4164: 4163: 4158: 4137: 4072:Transcriptional 4042: 4011: 3972: 3963:Polyadenylation 3934: 3908: 3873: 3867:Protein→Protein 3818: 3811: 3809:Gene expression 3806: 3764: 3759: 3712: 3708: 3655: 3651: 3616:Bird A (2002). 3614: 3610: 3555: 3551: 3520:(17): 7665–74. 3514:Mol. Cell. Biol 3506: 3502: 3463: 3459: 3443: 3442: 3438: 3424: 3420: 3388:10.1.1.376.5724 3371: 3367: 3322: 3318: 3269: 3265: 3232:(1): e1001773. 3218: 3214: 3169: 3165: 3120: 3116: 3091:10.1038/nrg3454 3079:Nat. Rev. Genet 3071: 3067: 3022: 3018: 2973: 2969: 2924: 2920: 2875: 2871: 2846:10.1038/nrm3951 2826: 2822: 2785: 2781: 2736: 2732: 2693: 2686: 2663:10.1038/nrg3207 2647: 2643: 2596: 2592: 2547: 2540: 2509:(11): 695–702. 2495: 2491: 2460:(17): R754–63. 2446: 2442: 2419:(Pt 2): 261–6. 2405: 2401: 2374: 2370: 2316: 2312: 2267: 2263: 2223: 2219: 2174: 2170: 2123: 2119: 2096:10.1038/nn.3151 2080: 2076: 2031: 2027: 1980: 1973: 1920: 1909: 1854: 1847: 1824:10.1038/nrg2538 1812:Nat. Rev. Genet 1808: 1801: 1764: 1755: 1718: 1714: 1669: 1665: 1634: 1630: 1599:(11): 5123–32. 1585: 1581: 1544: 1540: 1495: 1491: 1446: 1442: 1395: 1391: 1346: 1342: 1295: 1291: 1260: 1256: 1225:(17): R764–71. 1211: 1207: 1197: 1195: 1193:www.uniprot.org 1187: 1186: 1182: 1172: 1170: 1168:www.uniprot.org 1162: 1161: 1157: 1147: 1145: 1143:www.uniprot.org 1137: 1136: 1132: 1093: 1089: 1044: 1040: 1001: 997: 990: 976: 967: 963: 910: 904: 832:In eukaryotes, 830: 812: 751:phosphorylation 711: 700: 694: 691: 684: 675: 653: 649: 642: 625: 588:phosphorylation 567: 562: 457:groups, called 406: 367: 315: 303:Giemsa staining 279: 176: 28: 23: 22: 15: 12: 11: 5: 4188: 4178: 4177: 4160: 4159: 4157: 4156: 4151: 4149:François Jacob 4145: 4143: 4139: 4138: 4136: 4135: 4134: 4133: 4128: 4118: 4113: 4112: 4111: 4106: 4101: 4091: 4086: 4085: 4084: 4079: 4069: 4068: 4067: 4056: 4054: 4048: 4047: 4044: 4043: 4041: 4040: 4035: 4030: 4025: 4019: 4017: 4013: 4012: 4010: 4009: 4004: 3999: 3993: 3991: 3984: 3978: 3977: 3974: 3973: 3971: 3970: 3965: 3960: 3955: 3950: 3944: 3942: 3936: 3935: 3933: 3932: 3927: 3925:RNA polymerase 3922: 3916: 3914: 3910: 3909: 3907: 3906: 3901: 3896: 3890: 3888: 3881: 3875: 3874: 3872: 3871: 3870: 3869: 3864: 3859: 3849: 3848: 3847: 3829: 3823: 3821: 3813: 3812: 3805: 3804: 3797: 3790: 3782: 3776: 3775: 3770: 3763: 3762:External links 3760: 3758: 3757: 3706: 3649: 3608: 3549: 3500: 3457: 3437:978-0470917459 3436: 3418: 3365: 3336:(6): 1281–95. 3316: 3263: 3212: 3163: 3134:(11): 703–11. 3114: 3085:(6): 390–403. 3065: 3016: 2967: 2918: 2869: 2820: 2799:(4): 650–665. 2779: 2730: 2703:(8): 437–455. 2684: 2641: 2590: 2561:(6): 707–717. 2538: 2489: 2440: 2399: 2368: 2310: 2261: 2217: 2168: 2117: 2074: 2045:(2): 171–185. 2039:Neuroscientist 2025: 1971: 1907: 1845: 1799: 1778:(6): 1051–73. 1753: 1712: 1663: 1628: 1579: 1538: 1489: 1440: 1409:(5): 467–472. 1389: 1360:(4): 293–310. 1340: 1289: 1254: 1205: 1180: 1155: 1130: 1087: 1038: 995: 988: 964: 962: 959: 920:with numerous 906:Main article: 903: 900: 834:ribosomal rRNA 829: 826: 811: 808: 713: 712: 695:September 2021 656: 654: 647: 641: 638: 633:non-coding DNA 631:(CRM/CRE) are 624: 621: 600:ubiquitylation 566: 563: 561: 558: 405: 402: 366: 363: 347: 346: 343: 340: 278: 275: 250:RNA polymerase 218: 217: 214: 208: 205:RNA polymerase 189:RNA polymerase 175: 172: 118: 117: 116: 115: 103: 91: 83: 75: 67: 65:RNA polymerase 48: 35: 34: 26: 9: 6: 4: 3: 2: 4187: 4176: 4173: 4172: 4170: 4155: 4154:Jacques Monod 4152: 4150: 4147: 4146: 4144: 4140: 4132: 4129: 4127: 4124: 4123: 4122: 4119: 4117: 4116:Translational 4114: 4110: 4107: 4105: 4102: 4100: 4097: 4096: 4095: 4092: 4090: 4087: 4083: 4080: 4078: 4075: 4074: 4073: 4070: 4066: 4063: 4062: 4061: 4058: 4057: 4055: 4053: 4049: 4039: 4036: 4034: 4031: 4029: 4026: 4024: 4021: 4020: 4018: 4014: 4008: 4005: 4003: 4000: 3998: 3995: 3994: 3992: 3988: 3985: 3983: 3979: 3969: 3966: 3964: 3961: 3959: 3956: 3954: 3951: 3949: 3946: 3945: 3943: 3941: 3937: 3931: 3928: 3926: 3923: 3921: 3918: 3917: 3915: 3911: 3905: 3902: 3900: 3897: 3895: 3892: 3891: 3889: 3885: 3882: 3880: 3879:Transcription 3876: 3868: 3865: 3863: 3860: 3858: 3855: 3854: 3853: 3850: 3846: 3842: 3838: 3835: 3834: 3833: 3832:Central dogma 3830: 3828: 3825: 3824: 3822: 3820: 3814: 3810: 3803: 3798: 3796: 3791: 3789: 3784: 3783: 3780: 3774: 3771: 3769: 3766: 3765: 3753: 3749: 3744: 3739: 3734: 3729: 3725: 3721: 3717: 3710: 3702: 3698: 3693: 3688: 3684: 3680: 3676: 3672: 3668: 3664: 3660: 3653: 3645: 3641: 3636: 3631: 3627: 3623: 3619: 3612: 3604: 3600: 3595: 3590: 3585: 3580: 3576: 3572: 3569:(5): 1412–7. 3568: 3564: 3560: 3553: 3545: 3541: 3536: 3531: 3527: 3523: 3519: 3515: 3511: 3504: 3496: 3492: 3488: 3484: 3480: 3476: 3473:(5): 538–44. 3472: 3468: 3461: 3453: 3447: 3439: 3433: 3429: 3422: 3414: 3410: 3406: 3402: 3398: 3394: 3389: 3384: 3381:(3): 105–78. 3380: 3376: 3369: 3361: 3357: 3352: 3347: 3343: 3339: 3335: 3331: 3327: 3320: 3312: 3308: 3303: 3298: 3294: 3290: 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