303:
access. Histones are positively charged molecules which allow a tighter bonding to the negatively charged DNA molecule. Reducing the positive charge of histone proteins reduces the strength of binding between the histone and DNA, making it more open to gene transcription (expression). Moreover, these flexible units direct DNA wrapping in a left-handed manner around the histone octamer during nucleosome formation. Once the DNA is bound the tails continue to interact with the DNA. The parts of the tail closest to the DNA hydrogen bond and strengthen the DNA's association with the octamer; the parts of the tail furthest away from the DNA, however, work in a very different manner. Cellular enzymes modify the amino acids in the distal sections of the tail to influence the accessibility of the DNA. The tails have also been implicated in the stabilization of 30-nm fibers. Research has shown removing certain tails prevents the nucleosomes from forming properly and a general failure to produce chromatin fiber. In all, these associations protect the nucleosomal DNA from the external environment but also lower their accessibility to cellular replication and transcriptional machinery.
322:âinchwormâ fashion. In this method, using ATP as an energy source, the translocase domain of the nucleosome-remodeling complex detaches a small region of DNA from the histone octamer. This âwaveâ of DNA, spontaneously breaking and remaking the hydrogen bonds as it goes, then propagates down the nucleosomal DNA until it reaches the last binding site with the histone octamer. Once the wave reaches the end of the histone octamer the excess that was once at the edge is extended into the region of linker DNA. In total, one round of this method moves the histone octamer several base pairs in a particular directionâaway from the direction the âwaveâ propagated.
20:
344:
knockout mice have an open neural tube defect and therefore die before birth. p300â/â embryos exhibit defective development of the heart. CBP+/â mice display growth retardation, craniofacial abnormalities, hematological malignancies, which are not observed in mice with p300+/â. Mutations of both p300 have been reported in human tumors such as colorectal, gastric, breast, ovarian, lung, and pancreatic carcinomas. Also, activation or localization of two histone acetyltransferases can be oncogenic.
213:
114:
The structure of the octameric core complex was revisited seven years later and a resolution of 3.1 Ă
was elucidated for its crystal at a high salt concentration. Though sequence similarity is low between the core histones, each of the four have a repeated element consisting of a helix-loop-helix called the
317:
In order to access the nucleosomal DNA, the bonds between it and the histone octamer must be broken. This change takes place periodically in the cell as specific regions are transcribed, and it happens genome-wide during replication. Remodeling proteins work in three distinct ways: they can slide the
287:
side chains, respectively. Together these sites have a total of about 40 hydrogen bonds, most of which are from the backbone interactions. Additionally, 10 out of the 14 times that the minor groove faces the histone fold, an arginine side chain from the histone fold is inserted into the minor groove.
113:
theory has evolved. Chromatin subunit models as well as the notion of the nucleosome were established in 1973 and 1974, respectively. Richmond and his research group has been able to elucidate the crystal structure of the histone octamer with DNA wrapped up around it at a resolution of 7 Ă
in 1984.
618:
School, James D. Watson, Cold Spring Harbor
Laboratory, Tania A. Baker, Massachusetts Institute of Technology, Stephen P. Bell, Massachusetts Institute of Technology, Alexander Gann, Cold Spring Harbor Laboratory, Michael Levine, University of California, Berkeley, Richard Losik, Harvard University;
343:
activity. p300 and CBP are the most promiscuous histone acetyltransferase enzymes acetylating all four core histones on multiple residues. Lysine 18 and Lysine 27 on H3 were the only histone acetylation sites reduced upon CBP and p300 depletion in mouse embryonic fibroblasts. Also, CBP and p300
282:
The histone-fold domainsâ interaction with the minor groove accounts for the majority of the interactions in the nucleosome. As the DNA wraps around the histone octamer, it exposes its minor groove to the histone octamer at 14 distinct locations. At these sites, the two interact through a series of
228:
manner. In addition to compacting the DNA, the histone octamer plays a key role in the transcription of the DNA surrounding it. The histone octamer interacts with the DNA through both its core histone folds and N-terminal tails. The histone fold interacts chemically and physically with the DNA's
249:
enriched regions in the minor grooves. The N-terminal tails do not interact with a specific region of DNA but rather stabilize and guide the DNA wrapped around the octamer. The interactions between the histone octamer and DNA, however, are not permanent. The two can be separated quite easily and
163:
Quasi symmetry allows the heterodimer to be superimposed on itself by a 180 degree rotation around this symmetry axis. As a result of the rotation, two ends of histones involved in DNA binding of the crescent shape H3-H4 are equivalent, yet they organize different stretches of DNA. The H2A-H2B
321:
Of the three techniques, sliding is the most common and least extreme. The basic premise of the technique is to free up a region of DNA that the histone octamer would normally tightly bind. While the technique is not well defined, the most prominent hypothesis is that the sliding is done in an
302:
As mentioned above the histone tails have been shown to directly interact with the DNA of the nucleosome. Each histone in the octamer has an N-terminal tail that protrudes from the histone core. The tails play roles both in inter and intra nucleosomal interactions that ultimately influence gene
330:
Numerous reports show a link between age-related diseases, birth defects, and several types of cancer with disruption of certain histone post translational modifications. Studies have identified that N- and C-terminal tails are main targets for acetylation, methylation, ubiquitination and
155:
regions that are separated by disordered loops. The histone fold domain is responsible for formation of head-to-tail heterodimers of two histones: H2A-H2B and H3-H4. However, H3 and H4 histones first form a heterodimer and then in turn the heterodimer dimerizes to form a tetramer
151:. Heterodimers, or histone-only intermediates are formed from histone-fold domains. The formation of histone only-intermediates proceeds when core histones are paired into the interlocked crescent shape quasi-symmetric heterodimer. Each histone fold domain is composed of 3
283:
weak, non-covalent bonds. The main source of bonds comes from hydrogen bonds, both direct and water-mediated. The histone-fold hydrogen bonds with both phosphodiester backbone and the A:T rich bases. In these interactions, the histone fold binds to the oxygen atoms and
318:
DNA along the surface of the octamer, replace the one histone dimer with a variant, or remove the histone octamer entirely. No matter the method, in order to modify the nucleosomes, the remodeling complexes require energy from ATP hydrolysis to drive their actions.
146:
and the size or the protein ranges between 11400 and 15400 daltons, making them relatively small, yet highly positively charged proteins. High content of positively charged amino acids allow them to closely associate with negatively charged
331:
phosphorylation. New evidence is pointing to several modifications within the histone core. Research is turning towards deciphering the role of these histone core modifications at the histone-DNA interface in the chromatin.
567:
Davey, Curt A.; Sargent, David F.; Luger, Karolin; Maeder, Armin W.; Richmond, Timothy J. (June 2002). "Solvent
Mediated Interactions in the Structure of the Nucleosome Core Particle at 1.9Ă
Resolution".
274:. The positive charges allow them to closely associate with the negatively charged DNA through electrostatic interactions. Neutralizing the charges in the DNA allows it to become more tightly packed.
837:
Richmond, Timothy J.; Luger, Karolin; MĂ€der, Armin W.; Richmond, Robin K.; Sargent, David F. (18 September 1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution".
186:
indicates that after histone tails are removed, DNA is able to stay tightly bound to the nucleosome. Histone tails are subject to a wide array of modifications which includes
118:
motif. Furthermore, the details of protein-protein and protein-DNA interactions were fine-tuned by X-ray crystallography studies at 2.8 and 1.9 Ă
, respectively, in the 2000s.
1088:
1178:
696:
DâArcy, Sheena; Martin, Kyle W.; Panchenko, Tanya; Chen, Xu; Bergeron, Serge; Stargell, Laurie A.; Black, Ben E.; Luger, Karolin (September 2013).
644:
91:. These interactions keep the DNA and the histone octamer loosely associated, and ultimately allow the two to re-position or to separate entirely.
1129:
1241:
383:
Allfrey, VG; Mirsky, AE (May 1, 1964). "Structural
Modifications of Histones and their Possible Role in the Regulation of RNA Synthesis".
168:
tetramer is wrapped with DNA around it as a first step of nucleosome formation. Then two H2A-H2B dimers are connected to the DNA-(H3-H4)
258:. Specific remodeling proteins are constantly altering the chromatin structure by breaking the bonds between the DNA and nucleosome.
88:
160:. The heterodimer formation is based on the interaction of hydrophobic amino acid residue interactions between the two proteins.
175:
Each of the four core histones, in addition to their histone-fold domains, also contain flexible, unstructured extensions called
1097:"Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates"
560:
422:(1973). "Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease".
1187:"Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300"
1185:
Yao, TP; Oh, SP; Fuchs, M; Zhou, ND; Ch'ng, LE; Newsome, D; Bronson, RT; Li, E; Livingston, DM; Eckner, R (May 1, 1998).
698:"Chaperone Nap1 Shields Histone Surfaces Used in a Nucleosome and Can Put H2A-H2B in an Unconventional Tetrameric Form"
628:
510:"The nucleosomal core histone octamer at 3.1 ËA resolution: a tripartite protein assembly and a left-handed superhelix"
102:
1138:"Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation"
797:
Andrews, Andrew J.; Luger, Karolin (9 June 2011). "Nucleosome
Structure(s) and Stability: Variations on a Theme".
216:
The nucleosome assembles when DNA wraps around the histone octamer, two H2A-H2B dimers bound to an H3-H4 tetramer.
1136:
Jin, Q; Yu, LR; Wang, L; Zhang, Z; Kasper, LH; Lee, JE; Wang, C; Brindle, PK; Dent, SY; Ge, K (Jan 19, 2011).
134:
called H2A, H2B, H3 and H4 and they are all found in equal parts in the cell. All four of the core histone
332:
71:, containing two copies of H3 and two of H4, complexes with two H2A/H2B dimers. Each histone has both an
1261:
1056:
255:
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1051:
224:. Nucleosomes consist of a histone octamer surrounded by 146 base pairs of DNA wrapped in a
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were first identified and listed as having a potential regulatory role on the synthesis of
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8:
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Schiltz, RL; Mizzen, CA; Vassilev, A; Cook, RG; Allis, CD; Nakatani, Y (Jan 15, 1999).
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Klug; Richmond (1984). "Structure of the nucleosome core particle at 7 Ă
resolution".
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Biswas, Mithun; Voltz, Karine; Smith, Jeremy C.; Langowski, Jörg (15 December 2011).
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Harshman, S. W.; Young, N. L.; Parthun, M. R.; Freitas, M. A. (14 August 2013).
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623:(Seventh ed.). Boston: Benjamin-Cummings Publishing Company. p. 241.
419:
266:
Histones are composed of mostly positively charged amino acid residues such as
661:
Luger, Karolin (April 2003). "Structure and dynamic behavior of nucleosomes".
1250:
695:
534:
84:
1065:
651:
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The other four times, the arginine comes from a tail region of the histone.
1171:
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1003:"Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism"
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The nucleosome core particle is the most basic form of DNA compaction in
195:
191:
56:
52:
1042:
Jenuwein, T; Allis, CD (Aug 10, 2001). "Translating the histone code".
353:
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233:. Studies have found that the histones interact more favorably with
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271:
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180:
143:
131:
127:
68:
858:
954:"NEW EMBO MEMBER'S REVIEW: Nucleosome sliding: facts and fiction"
895:"Role of Histone Tails in Structural Stability of the Nucleosome"
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in its own way through a series of weak interactions, including
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histone-fold. Each of these key components interacts with
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201:
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47:. It consists of two copies of each of the four core
1000:
747:"H1 histones: current perspectives and challenges"
619:with Stephen C. Harrison, Harvard Medical (2014).
1238:HistoneDB 2.0 - Database of histones and variants
1041:
382:
16:8-protein complex forming the core of nucleosomes
1248:
507:
417:
663:Current Opinion in Genetics & Development
109:in 1964. Since then, over several decades,
643:: CS1 maint: multiple names: authors list (
456:
335:and cAMP response element-binding protein (
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1001:Fazzio, TG; Tsukiyama, T (November 2003).
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198:of serine, lysine and arginine residues.
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179:âtailsâ. Treatment of nucleosomes with
164:dimer also folds similarly. The (H3-H4)
138:sequences contain between 20 and 24% of
18:
787:
122:The histone octamer in molecular detail
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811:10.1146/annurev-biophys-042910-155329
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307:Nucleosome remodeling and disassembly
202:The histone octamer in the nucleosome
1101:The Journal of Biological Chemistry
952:Becker, P. B. (16 September 2002).
450:
292:Tail interactions and modifications
13:
278:Interactions with the minor groove
14:
1273:
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103:post-translational modifications
67:). The octamer assembles when a
994:
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172:complex to form a nucleosome.
1:
1204:10.1016/S0092-8674(00)81165-4
1020:10.1016/s1097-2765(03)00436-2
675:10.1016/S0959-437X(03)00026-1
621:Molecular biology of the gene
582:10.1016/S0022-2836(02)00386-8
424:Biochem. Biophys. Res. Commun
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920:10.1371/journal.pcbi.1002279
714:10.1016/j.molcel.2013.07.015
570:Journal of Molecular Biology
436:10.1016/0006-291x(73)90740-7
397:10.1126/science.144.3618.559
7:
799:Annual Review of Biophysics
508:Arents; Burlingame (1991).
347:
10:
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899:PLOS Computational Biology
310:
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43:found at the center of a
535:10.1073/pnas.88.22.10148
262:Histone/DNA interactions
45:nucleosome core particle
1066:10.1126/science.1063127
1154:10.1038/emboj.2010.318
1114:10.1074/jbc.274.3.1189
751:Nucleic Acids Research
241:enriched regions than
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311:Further information:
296:Further information:
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206:Further information:
39:is the eight-protein
22:
970:10.1093/emboj/cdf486
313:Chromatin remodeling
911:2011PLSCB...7E2279B
851:1997Natur.389..251L
526:1991PNAS...8810148A
471:1984Natur.311..532R
95:History of research
763:10.1093/nar/gkt700
420:Burgoyne, Leigh A.
339:) possess histone
326:Clinical relevance
218:
29:
1262:Molecular biology
1050:(5532): 1074â80.
964:(18): 4749â4753.
845:(6648): 251â260.
757:(21): 9593â9609.
465:(5986): 532â537.
418:Hewish, Dean R.;
341:acetyltransferase
250:often are during
33:molecular biology
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23:Basic units of
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1232:External links
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1057:10.1.1.453.900
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1007:Molecular Cell
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702:Molecular Cell
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231:minor groove
226:superhelical
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116:histone fold
98:
89:salt bridges
36:
30:
252:replication
196:methylation
192:acetylation
75:tail and a
1251:Categories
370:References
354:Nucleosome
222:eukaryotes
208:Nucleosome
136:amino acid
77:C-terminal
73:N-terminal
51:proteins (
1052:CiteSeerX
639:cite book
364:Chromatin
130:are four
111:chromatin
27:structure
25:chromatin
1257:Proteins
1172:21131905
1074:11498575
1029:14636590
988:12234915
939:22207822
819:21332355
781:23945933
732:23973327
683:12672489
590:12079350
405:17836360
348:See also
285:hydroxyl
272:arginine
181:protease
144:arginine
132:proteins
128:histones
69:tetramer
1213:9590171
1163:3025463
1123:9880483
1082:1883924
1044:Science
930:3240580
907:Bibcode
875:4328827
867:9305837
847:Bibcode
772:3834806
723:3878309
554:1946434
522:Bibcode
495:4355982
487:6482966
467:Bibcode
444:4711166
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