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Briefings in Functional Genomics and Proteomics 2006 5(3):222-227; doi:10.1093/bfgp/ell030
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Special Issue Papers

Epigenetic regulators and histone modification

Axel Imhof

Axel Imhof, Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, Schillerstr. 44, 80336 Muenchen Germany. Tel: +49 89 218075 420; Fax: +49 89 218075 440; E-mail: imhof{at}lmu.de


   ABSTRACT
TOP
 ABSTRACT
HISTONE MODIFICATIONS
 TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
 Acknowledgement
 References
 
Epigenetic inheritance is a key element in the adaptation of organisms to a rapidly changing environment without stably changing their DNA sequence. The necessary changes in its gene expression profiles are frequently associated with variations in chromatin structure. The conformation of chromatin is profoundly influenced by the post-translational modification of the histone proteins, the incorporation of histone variants, the activity of nucleosome remodelling factors and the association of non-histone chromatin proteins. Although the hierarchy of these factors is still not fully understood, genetic experiments suggest that histone-modifying enzymes play a major causal role in setting up a particular chromatin structure. In this article, the recent progress that was made to understand the molecular mechanisms of the targeting and regulation of histone modifiers and its implication for epigenetic inheritance are reviewed.

Keywords: chromatin, post-translational modifications, epigenetics, methylation

The term ‘epigenetics’ literally means ‘besides genetics’ and is commonly used to describe heritable alterations of phenotypic traits that are not based on changes in DNA sequence. In the literature it is used to explain many aspects of the transmission of genetic information ranging from the mitotically stable silencing of whole chromosomes [1–3] over the tissue specific maintenance of gene activity [4–6] to the heritable affect of nutrition on gene expression patterns [7, 8]. What all those divergent fields have in common is that a particular gene expression pattern is established by extrinsic or intrinsic factors, and is subsequently maintained through several cell divisions and sometimes even through meiosis making it an important evolutionary driver.

Frequently (but not always [9, 10]), these epigenetic changes are associated with stable changes in chromatin structure. The conformational changes of chromatin structure have been mostly studied using their differential accessibility to nucleases or RNA polymerases [11–14] and by various microscopic techniques [15]. The detailed molecular structure of chromatin in the eukaryotic nucleus, however, is still enigmatic. Over the last few years considerable progress has been made to characterize the structure of chromatin fibres in the test tube [16–19], suggesting that the intranucleosomal interactions of the histone tails have a substantial impact on the folding of higher order chromatin structure.

The N-terminal tails of the four core histones do not contribute to the formation of the nucleosomal core particle in vitro, and do not adopt a defined structure in the crystal of a mononucleosome [20]. However, the amino acid sequence of these N-terminal tails is highly evolutionary conserved. This extraordinary degree of preservation points to a strong selective force to maintain the sequence of the N-termini. One possible explanation for this conservation is the fact that the tails carry multiple post-translational modifications. The modifications in turn can then substantially influence chromatin structure.


   HISTONE MODIFICATIONS
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 ABSTRACT
 HISTONE MODIFICATIONS
TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
 Acknowledgement
 References
 
Studies on mononucleosomes as well as on nucleosomal arrays show for example that the acteylation of lysines within the tails facilitates the binding of transcription factors [21, 22], and disrupts the folding of nucleosomal fibres [23, 24]. Deletion of the N-termini of H3 and H4 is lethal in yeast [25], and the mutation of individual lysine residues leads to changes in gene expression patterns [26] that are enhanced when multiple lysines are mutated. In this study, the contribution of an individual lysine acetylation to establish a specific gene expression pattern is limited. Therefore, the findings do not support a model in which a complex combinatorial code is involved in setting up particular gene expression patterns. This interpretation is supported by a high resolution mapping, of modification patterns, of yeast mononucleosomes [27] that shows a rather low complexity of different modification patterns. However, the situation may be different in higher eukaryotes. Studies on polytene chromosomes of Drosophila melanogaster show a clear enrichment of H4K16ac on the male hyperactive X chromosome [28] and an enrichment of H4K12ac in inactive regions [28].

Although histone acetylation seems to be a good candidate to mark specific regions for transcriptional activation, because of its direct effect on chromatin structure, it is hard to reconcile the presence of this rather transient modification (t1/2 = 3–30 min [29]) with the establishment of stable gene expression patterns that can be transmitted through cell divisions. In fact, no acetyltransferase has been isolated so far as genetic modifier in screens using stable gene expression patterns as a readout system. Acetylation does, however, have an impact on the establishment of stable gene expression patterns as a transient pulse of histone acetylation can switch on the expression of a transgene in Drosophila embryos, whose expression state can then be maintained over several cell generations [30]. This effect is dependent on the presence of a specific DNA element, within the transgenic construct, and a set of transcriptional regulators that play an important role in the maintenance of the tissue specific homeobox gene expression. The DNA elements are frequently called PREs or trithorax response elements (TREs) for polycomb and trithorax response elements or cellular memory modules (CMMs) [6, 31, 32]. Those short regions, on the DNA, are critical for establishing specialized chromatin structures that either repress or activate the neighbouring transcription units in a heritable manner. A heterogeneous set of chromatin-associated proteins is required to maintain this state either in a repressed state [the polycomb group (Pc-G) factors] or an activated state [the trithorax group (Trx-G)]. Both groups contain enzymes that are able to specifically modify the histone tails. However, in contrast to the acetyltransferases that generate modifications with a high turnover rate, the histone modifying enzymes that are found in the Pc-or Trx-G have mainly histone methyltransferase (HMT) activity. HMTases methylate lysine residues within the histone tails (arginine residues are methylated by enzymes that belong to the PRMT family [33], and can add up to three methyl groups per individual lysine. The slow turnover rate of methylated lysines [34] makes this modification a perfect candidate for maintaining a stable chromatin state through several cell divisions, and therefore, a key player in epigenetic inheritance. For a long time histone methylation has been considered irreversible, being reversed only by the exchange of methylated histones with unmethylated ones [35] or by proteolytic cleavage of the tail [36, 37]. However, more recently several histone demethylases have been shown to actively remove methyl groups methylated histones through an oxidative mechanism [38–40].


   TARGETING OF MODIFIERS
TOP
 ABSTRACT
 HISTONE MODIFICATIONS
 TARGETING OF MODIFIERS
RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
 Acknowledgement
 References
 
In order to serve as a mark that has the potential to distinguish different regions of the genome the modifications have to be directed to specific loci. There are several ways of targeting modifying enzymes to their site of action (Figure 1). The most intuitive one is probably the targeting by an interaction with sequence specific transcription factors. This leads to a more localized modification that can in extreme cases be limited to a single nucleosome at the promoter [41] of a given gene. Such a targeting mechanism has been shown for acetyltransferases [42–44], deacetylases [45, 46], methyltransferases [47–49] and also more recently demethylases [38, 40]. Besides this very specific action, histone-modifying enzymes have also been shown to interact with proteins that track the DNA such as the RNA polymerases [50–52] or the replication clamp proliferating cell nuclear antigen (PCNA) [53], which leads to a modification of larger genomic loci in the process.


Figure 1
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  		Figure 1: Targeting mechanisms for histone modifications. Histone modification patterns can be established over defined chromosomal regions by multiple mechanisms. All targeting systems require a targeting molecule that could bind a DNA sequence like many sequence-specific transcription factors (a). Recognize a specific modification (b). Or a non-translated RNA molecule (c). The targeting molecule can then selectively interact with a specific histone modifier to set up a defined histone modification pattern.

 
More recently, a third mechanism of targeting histone-modifying activities has been proposed that involves the transcription of non-translated RNAs from the corresponding gene locus. The inactivation of the mammalian X-chromosome as well as the hyperactivation of the male X-chromosome in dipterans for example are both crucially dependent on the presence of a RNA molecule, which in turn is important for the accumulation of specific modification marks on the whole chromosome [54–57]. Also the transcriptional repression of peri-centromeric DNA is dependent of the RNAi machinery that helps targeting the methylation of H3K9 to this chromosomal domain. Elegant experiments in Schizzosacharomyces pombe showed that the RNAi machinery is important for the establishment but not the maintenance of centromeric heterochromatin [58–60]. The subsequent biochemical characterization of the protein complex responsible for RNAi induced transcriptional silencing, the repeat induced transcriptional silencing (RITS) complex showed that it contains another chromo domain protein that is able to interact with H3K9me suggesting a very intricate relationship between dsRNA, histone methylation and heterochromatin formation [58, 61]. With the discovery of the RNAi mediated transcriptional silencing complex and the involvement of the RNAi machinery in the heterochromatin formation, many of the RNA molecules that are derived from intergenic transcription have gained considerable attention. Even in the already discussed classical epigenetically inherited expression profile of homeobox genes, the binding of a RNA molecule has been shown to play a crucial role in the targeting of a HMT to their site of action [62]. In this case, the HMT Ash1 that belongs to the Trx-G requires active transcription from the TRE to be targeted to a specific area. Ash1 itself binds to RNA, which provides a good example for the targeting of a functionally active histone-modifying enzyme. These selected examples already show that the histone modifying enzymes can be selectively targeted to distinct loci within the genome by various mechanisms, ranging from the ability to modify small regions of just a few nucleosomes to whole chromosomes such as the inactive female X-chromosome in mammals or the hyperactive male X-chromosome in fruit flies.


   RECOGNITION OF MODIFICATIONS
TOP
 ABSTRACT
 HISTONE MODIFICATIONS
 TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
NOTE ADDED IN PROOF
 Acknowledgement
 References
 
How are the modifications then translated into a defined chromatin structure, which can then subsequently lead to an epigenetic change? In the case of histone acetylation, the modification in itself changes the physicochemical properties of the chromatin fibre such that an acetylated array adopts a more open conformation. However, histone methylation clearly does not have such an effect on chromatin folding. What was found however, is that the various modifications can be recognized by non-chromatin proteins that can either lead to a structural change in chromatin such as the heterochromatin protein 1 (HP1) that is thought to stabilize a condensed higher order structure [16], enzymes that can either mobilize nucleosomes [63, 64], modify the associated DNA [65] or further modify the histones [66–68]. The two classes of domains that are found to interact strongly with specific chromatin modifications can be categorized into the chromodomain or tudor superfamily [69] that binds preferentially methylated lysine residues and the bromo domain family that recognizes acetylated lysines [70]. However, the ability to recognize specific marks does not seem to be exclusive to these domains as it has recently been shown that another domain that is commonly found in chromatin associated factors, the WD40 domain also possesses the ability to interact selectively with methylated lysine residues [71]. In this respect it is also important to mention that many chromatin associated factors contain several domains that can potentially interact with modified chromatin. This may suggest that these factors can indeed read a particular modification pattern on histones by binding to a complex combination of modification. However, the affinities of the factors to the modified tails in vitro are relatively weak, therefore, the contribution of a modification to a specific association with chromatin is probably not the only one [72, 73].

Especially, the discoveries of protein domains that are able to recognize specific modifications or combinations thereof make the histone code hypothesis are very attractive model to explain epigenetic inheritance [74]. The hypothesis was initially proposed by Turner and colleagues [75], and suggests that different histone modifications code for specific chromatin conformations. These different modifications could act in a combinatorial manner and heritably alter gene expression without a change in the DNA sequence. As the nucleosomes immediately reassociate with the newly replicated DNA, the modification patterns can potentially be transmitted through several rounds of cell divisions and maintain the chromatin structure. Although this is a very appealing model, experiments in yeast do not support the idea of a complex combinatorial code but rather suggest a simple on–off switch with chromatin being either in an open or a closed conformation [26, 76]. It remains to be seen whether this is also true in the case of higher eukaryotes and more complex modifications. In summary, one can conclude that our understanding of the exact way how particular modification patterns are established and maintained is still very preliminary. Genetic experiments such as screens for modifiers of position effect variegation or regulators of Hox-expression have led to the identification of a large number of factors that participate in the establishment of a defined functional state of the underlying chromatin. The next challenge will be the deciphering of the precise mechanisms that allow those factors to set up a specific structure. One key to do this will be the reconstitution of distinct chromatin structures in the test tube by sequentially adding all the necessary factors. The analysis of all the necessary and sufficient players to set up a defined structure in vitro should then allow us to develop and test a model of how epigenetic signals are set and interpreted in vivo.


   NOTE ADDED IN PROOF
TOP
 ABSTRACT
 HISTONE MODIFICATIONS
 TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
Acknowledgement
 References
 
However, while the manuscript was under review, crystallographic studies using the WD40 domain of WDR5 showed that it is able to bind the H3 N-terminus irrespective of its methylation state. Instead of ‘reading’ a modification state the domain has how been suggested to present the tail to the modifying enzyme [77, 78].


Key Points

  • Post-translational modifications on Histones play an important role for epigenetic inheritance.
  • Methylation of lysines plays a key role in setting up patterns of PTMs.
  • The targeting of modifying enzymes is mediated by diverse mechanisms. Certain chromatin proteins can recognize specific modifications.

 


   Acknowledgement
TOP
 ABSTRACT
 HISTONE MODIFICATIONS
 TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
 Acknowledgement
References
 
The author would like to thank Josephine Sutcliffe for useful comments on the manuscript and help during its preparation.


   FOOTNOTES
 
Axel Imhof studied biology at the University of Regensburg and received his Diploma in 1992. He entered graduate school at the University Regensburg and finished his doctoral thesis in 1995 at the Institute of Pathology. After a 3-year post-doctoral period at the NIH he became an independent group leader at the Adolf-Butenandt Institute of the University of Munich.


   References
TOP
 ABSTRACT
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 TARGETING OF MODIFIERS
 RECOGNITION OF MODIFICATIONS
 NOTE ADDED IN PROOF
 Acknowledgement
 References
 

  1. Heard E. Recent advances in X-chromosome inactivation. Curr Opin Cell Biol 2004; 16:247–55.[CrossRef][Web of Science][Medline]
  2. Jablonka E. The evolution of the peculiarities of mammalian sex chromosomes: an epigenetic view. Bioessays 2004; 26:1327–32.[CrossRef][Web of Science][Medline]
  3. Schutt C, Nothiger R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development 2000; 127:667–77.[Abstract]
  4. Orlando V. Polycomb, epigenomes, and control of cell identity. Cell 2003; 112:599–606.[CrossRef][Web of Science][Medline]
  5. Bernstein E, Allis CD. RNA meets chromatin. Genes Dev 2005; 19:1635–55.[Abstract/Free Full Text]
  6. Ringrose L, Paro R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 2004; 38:413–43.[CrossRef][Web of Science][Medline]
  7. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003; 33:Suppl, 245–54.[CrossRef][Web of Science][Medline]
  8. Oommen AM, Griffin JB, Sarath G, et al. Roles for nutrients in epigenetic events. J Nutr Biochem 2005; 16:74–7.[CrossRef][Web of Science][Medline]
  9. Wickner RB, Edskes HK, Roberts BT, et al. Prions of yeast as epigenetic phenomena: high protein "copy number" inducing protein "silencing". Adv Genet 2002; 46:485–25.[Web of Science][Medline]
  10. True HL, Berlin I, Lindquist SL. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 2004; 431:184–7.[CrossRef][Medline]
  11. Krebs JE, Peterson CL. Understanding "active" chromatin: a historical perspective of chromatin remodeling. Crit Rev Eukaryot Gene Expr 2000; 10:1–12.[Web of Science][Medline]
  12. Felsenfeld G, Boyes J, Chung J, et al. Chromatin structure and gene expression. Proc Natl Acad Sci USA 1996; 93:9384–8.[Abstract/Free Full Text]
  13. Fitzgerald DP, Bender W. Polycomb group repression reduces DNA accessibility. Mol Cell Biol 2001; 21:6585–97.[Abstract/Free Full Text]
  14. McCall K, Bender W. Probes of chromatin accessibility in the Drosophila bithorax complex respond differently to Polycomb-mediated repression. Embo J 1996; 15:569–80.[Web of Science][Medline]
  15. Zink D, Sadoni N, Stelzer E. Visualizing chromatin and chromosomes in living cells. Methods 2003; 29:42–50.[CrossRef][Web of Science][Medline]
  16. Fan JY, Rangasamy D, Luger K, et al. H2A.Z alters the nucleosome surface to promote HP1alpha-mediated chromatin fiber folding. Mol Cell 2004; 16:655–61.[CrossRef][Web of Science][Medline]
  17. Ausio J. Analytical ultracentrifugation and the characterization of chromatin structure. Biophys Chem 2000; 86:141–53.[CrossRef][Web of Science][Medline]
  18. Schalch T, Duda S, Sargent DF, et al. X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature 2005; 436:138–41.[CrossRef][Medline]
  19. Huynh VA, Robinson PJ, Rhodes D. A method for the in vitro reconstitution of a defined "30 nm" chromatin fibre containing stoichiometric amounts of the linker histone. J Mol Biol 2005; 345:957–68.[CrossRef][Web of Science][Medline]
  20. Luger K, Mader AW, Richmond RK, et al. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 1997; 389:251–60.[CrossRef][Medline]
  21. Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 1993; 72:73–84.[CrossRef][Web of Science][Medline]
  22. Vettese-Dadey M, Grant PA, Hebbes TR, et al. Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. Embo J 1996; 15:2508–18.[Web of Science][Medline]
  23. Garcia-Ramirez M, Rocchini C, Ausio J. Modulation of chromatin folding by histone acetylation. J Biol Chem 1995; 270:17923–8.[Abstract/Free Full Text]
  24. Tse C, Sera T, Wolffe AP, et al. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Mol Cell Biol 1998; 18:4629–38.[Abstract/Free Full Text]
  25. Ling X, Harkness TA, Schultz MC, et al. Yeast histone H3 and H4 amino termini are important for nucleosome assembly in vivo and in vitro: redundant and position-independent functions in assembly but not in gene regulation. Genes Dev 1996; 10:686–99.[Abstract/Free Full Text]
  26. Dion MF, Altschuler SJ, Wu LF, et al. Genomic characterization reveals a simple histone H4 acetylation code. Proc Natl Acad Sci USA 2005; 102:5501–6.[Abstract/Free Full Text]
  27. Liu CL, Kaplan T, Kim M, et al. Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol 2005; 3:e328.[CrossRef][Medline]
  28. Turner BM, Birley AJ, Lavender J. Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell 1992; 69:375–84.[CrossRef][Web of Science][Medline]
  29. Jackson V, Shires A, Chalkley R, et al. Studies on highly metabolically active acetylation and phosphorylation of histones. J Biol Chem 1975; 250:4856–63.[Abstract/Free Full Text]
  30. Cavalli G, Paro R. Epigenetic inheritance of active chromatin after removal of the main transactivator. Science 1999; 286:955–8.[Abstract/Free Full Text]
  31. Pirrotta V, Poux S, Melfi R, et al. Assembly of Polycomb complexes and silencing mechanisms. Genetica 2003; 117:191–7.[CrossRef][Web of Science][Medline]
  32. Cavalli G. Chromatin as a eukaryotic template of genetic information. Curr Opin Cell Biol 2002; 14:269–78.[CrossRef][Web of Science][Medline]
  33. Sims RJ III, Nishioka K, Reinberg D. Histone lysine methylation: a signature for chromatin function. Trends Genet 2003; 19:629–39.[CrossRef][Web of Science][Medline]
  34. Waterborg JH. Dynamic methylation of alfalfa histone H3. J Biol Chem 1993; 268:4918–21.[Abstract/Free Full Text]
  35. Ahmad K, Henikoff S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 2002; 9:1191–200.[CrossRef][Web of Science][Medline]
  36. Allis CD, Bowen JK, Abraham GN, et al. Proteolytic processing of histone H3 in chromatin: a physiologically regulated event in Tetrahymena micronuclei. Cell 1980; 20:55–64.[CrossRef][Web of Science][Medline]
  37. Schneider R, Bannister AJ, Weise C, et al. Direct binding of INHAT to H3 tails disrupted by modifications. J Biol Chem 2004; 279:23859–62.[Abstract/Free Full Text]
  38. Yamane K, Toumazou C, Tsukada YI, et al. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 2006; 125:438–95.
  39. Tsukada Y, Fang J, Erdjument-Bromage H, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature 2006; 439:811–6.[CrossRef][Medline]
  40. Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004; 119:941–53.[CrossRef][Web of Science][Medline]
  41. Agalioti T, Lomvardas S, Parekh B, et al. Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter. Cell 2000; 103:667–78.[CrossRef][Web of Science][Medline]
  42. Imhof A, Wolffe AP. Transcription: gene control by targeted histone acetylation. Curr Biol 1998; 8:R422–4.[CrossRef][Web of Science][Medline]
  43. Howe L, Brown CE, et al. Histone acetyltransferase complexes and their link to transcription. Crit Rev Eukaryot Gene Expr 1999; 9:231–43.[Web of Science][Medline]
  44. McManus KJ, Hendzel MJ. CBP, a transcriptional coactivator and acetyltransferase. Biochem Cell Biol 2001; 79:253–66.[CrossRef][Web of Science][Medline]
  45. Kiermaier A, Eilers M. Transcriptional control: calling in histone deacetylase. Curr Biol 1997; 7:R505–7.[CrossRef][Web of Science][Medline]
  46. Wolffe AP. Histone deacetylase: a regulator of transcription. Science 1996; 272:371–2.[CrossRef][Web of Science][Medline]
  47. Nielsen SJ, Schneider R, Bauer UM, et al. Rb targets histone H3 methylation and HP1 to promoters. Nature 2001; 412:561–5.[CrossRef][Medline]
  48. Stewart MD, Li J, Wong J. Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol Cell Biol 2005; 25:2525–38.[Abstract/Free Full Text]
  49. Snowden AW, Gregory PD, Case CC, et al. Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr Biol 2002; 12:2159–66.[CrossRef][Web of Science][Medline]
  50. Krogan NJ, Kim M, Tong A, et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol 2003; 23:4207–18.[Abstract/Free Full Text]
  51. Krogan NJ, Dover J, Wood A, et al. The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell 2003; 11:721–9.[CrossRef][Web of Science][Medline]
  52. Ng HH, Robert F, Young RA, et al. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 2003; 11:709–19.[CrossRef][Web of Science][Medline]
  53. Sarraf SA, Stancheva I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell 2004; 15:595–605.[CrossRef][Web of Science][Medline]
  54. Silva J, Mak W, Zvetkova I, et al. Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell 2003; 4:481–95.[CrossRef][Web of Science][Medline]
  55. Cao R, Zhang Y. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 2004; 14:155–64.[CrossRef][Web of Science][Medline]
  56. Plath K, Fang J, Mlynarczyk-Evans SK, et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 2003; 300:131–5.[Abstract/Free Full Text]
  57. Rougeulle C, Chaumeil J, Sarma K, et al. Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X chromosome. Mol Cell Biol 2004; 24:5475–84.[Abstract/Free Full Text]
  58. Verdel A, Jia S, Gerber S, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 2004; 303:672–6.[Abstract/Free Full Text]
  59. Hall IM, Shankaranarayana GD, Noma K, et al. Establishment and maintenance of a heterochromatin domain. Science 2002; 297:2232–7.[Abstract/Free Full Text]
  60. Volpe TA, Kidner C, Hall IM, et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 2002; 297:1833–7.[Abstract/Free Full Text]
  61. Noma K, Sugiyama T, Cam H, et al. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat Genet 2004; 36:1174–80.[CrossRef][Web of Science][Medline]
  62. Sanchez-Elsner T, Gou D, Kremmer E, et al. Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science 2006; 311:1118–23.[Abstract/Free Full Text]
  63. Zegerman P, Canas B, Pappin D, et al. Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J Biol Chem 2002; 277:11621–4.[Abstract/Free Full Text]
  64. Kasten M, Szerlong H, Erdjument-Bromage H, et al. Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14. Embo J 2004; 23:1348–59.[CrossRef][Web of Science][Medline]
  65. Lindroth AM, Shultis D, Jasencakova Z, et al. Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. Embo J 2004; 23:4286–96.[CrossRef][Medline]
  66. Rea S, Eisenhaber F, O'Carroll D, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 2000; 406:593–9.[CrossRef][Medline]
  67. Huang Y, Fang J, Bedford MT, et al. Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A. Science 2006; 312:748–51.[Abstract/Free Full Text]
  68. Hassan AH, Prochasson P, Neely KE, et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 2002; 111:369–79.[CrossRef][Web of Science][Medline]
  69. Maurer-Stroh S, Dickens NJ, Hughes-Davies L, et al. The Tudor domain ‘Royal Family’: Tudor, plant Agenet, Chromo, PWWP and MBT domains. Trends Biochem Sci 2003; 28:69–74.[CrossRef][Web of Science][Medline]
  70. Hudson BP, Martinez-Yamout MA, Dyson HJ, et al. Solution structure and acetyl-lysine binding activity of the GCN5 bromodomain. J Mol Biol 2000; 304:355–70.[CrossRef][Web of Science][Medline]
  71. Wysocka J, Swigut T, Milne TA, et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 2005; 121:859–72.[CrossRef][Web of Science][Medline]
  72. Jacobs SA, Khorasanizadeh S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 2002; 295:2080–3.[Abstract/Free Full Text]
  73. Jacobson RH, Ladurner AG, King DS, et al. Structure and function of a human TAFII250 double bromodomain module. Science 2000; 288:1422–5.[Abstract/Free Full Text]
  74. Jenuwein T, Allis CD. Translating the histone code. Science 2001; 293:1074–80.[Abstract/Free Full Text]
  75. Turner BM. Histone acetylation and an epigenetic code. Bioessays 2000; 22:836–45.[CrossRef][Web of Science][Medline]
  76. Henikoff S. Histone modifications: combinatorial complexity or cumulative simplicity? Proc Natl Acad Sci USA 2005; 102:5308–9.[Free Full Text]
  77. Couture JF, Collazo E, Trievel RC. Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol 2006; 13:698–703.[CrossRef][Web of Science][Medline]
  78. Ruthenburg AJ, Wang W, Graybosch DM, et al. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol 2006; 13:704–12.[CrossRef][Web of Science][Medline]

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