The diverse functions of histone lysine methylation

Covalent modifications of histone tails have fundamental roles in chromatin structure and function. One such modification, lysine methylation, has important functions in many biological processes that include heterochromatin formation, X-chromosome inactivation and transcriptional regulation. Here, we summarize recent advances in our understanding of how lysine methylation functions in these diverse biological processes, and raise questions that need to be addressed in the future.

[1]  G. Reuter,et al.  The protein encoded by the Drosophila position‐effect variegation suppressor gene Su(var)3‐9 combines domains of antagonistic regulators of homeotic gene complexes. , 1994, The EMBO journal.

[2]  B. Wakimoto,et al.  Heterochromatin and gene expression in Drosophila. , 1995, Annual review of genetics.

[3]  E. Nimmo,et al.  Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function. , 1996, Journal of cell science.

[4]  B. Wakimoto,et al.  Beyond the Nucleosome: Epigenetic Aspects of Position–Effect Variegation in Drosophila , 1998, Cell.

[5]  M. Grunstein Yeast Heterochromatin: Regulation of Its Assembly and Inheritance by Histones , 1998, Cell.

[6]  Lei Zeng,et al.  Structure and ligand of a histone acetyltransferase bromodomain , 1999, Nature.

[7]  G. Schotta,et al.  Functional mammalian homologues of the Drosophila PEV‐modifier Su(var)3‐9 encode centromere‐associated proteins which complex with the heterochromatin component M31 , 1999, The EMBO journal.

[8]  R. Kornberg,et al.  Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome , 1999, Cell.

[9]  R. Kingston,et al.  Stabilization of Chromatin Structure by PRC1, a Polycomb Complex , 1999, Cell.

[10]  R. Allshire,et al.  Distinct protein interaction domains and protein spreading in a complex centromere. , 2000, Genes & development.

[11]  B M Turner,et al.  Histone acetylation and an epigenetic code. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[12]  R. Tjian,et al.  Structure and function of a human TAFII250 double bromodomain module. , 2000, Science.

[13]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[14]  S. Elgin,et al.  The HP1 protein family: getting a grip on chromatin. , 2000, Current opinion in genetics & development.

[15]  J. Hansen,et al.  The Core Histone N Termini Function Independently of Linker Histones during Chromatin Condensation* , 2000, The Journal of Biological Chemistry.

[16]  C. Ponting,et al.  Regulation of chromatin structure by site-specific histone H3 methyltransferases , 2000, Nature.

[17]  T. Magnuson,et al.  Imprinted X inactivation maintained by a mouse Polycomb group gene , 2001, Nature Genetics.

[18]  Andrew J. Bannister,et al.  Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain , 2001, Nature.

[19]  R. Kornberg,et al.  A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Karl Mechtler,et al.  Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins , 2001, Nature.

[21]  C. Ponting,et al.  JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2beta. , 2001, Trends in biochemical sciences.

[22]  E. Selker,et al.  A histone H3 methyltransferase controls DNA methylation in Neurospora crassa , 2001, Nature.

[23]  D. Reinberg,et al.  Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. , 2001, Genes & development.

[24]  Brian D. Strahl,et al.  Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly , 2001, Science.

[25]  Andrew J. Bannister,et al.  Rb targets histone H3 methylation and HP1 to promoters , 2001, Nature.

[26]  M. Stallcup,et al.  Role of protein methylation in chromatin remodeling and transcriptional regulation , 2001, Oncogene.

[27]  J. Davie,et al.  Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. , 2001, Genes & development.

[28]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[29]  Stuart L. Schreiber,et al.  Active genes are tri-methylated at K4 of histone H3 , 2002, Nature.

[30]  V. Pirrotta,et al.  Drosophila Enhancer of Zeste/ESC Complexes Have a Histone H3 Methyltransferase Activity that Marks Chromosomal Polycomb Sites , 2002, Cell.

[31]  Zu-Wen Sun,et al.  Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast , 2002, Nature.

[32]  Paul Tempst,et al.  PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. , 2002, Molecular cell.

[33]  G. Poirier,et al.  Disruptor of Telomeric Silencing-1 Is a Chromatin-specific Histone H3 Methyltransferase* , 2002, The Journal of Biological Chemistry.

[34]  Brigitte Wild,et al.  Histone Methyltransferase Activity of a Drosophila Polycomb Group Repressor Complex , 2002, Cell.

[35]  Tony Kouzarides,et al.  cis-Acting DNA from Fission Yeast Centromeres Mediates Histone H3 Methylation and Recruitment of Silencing Factors and Cohesin to an Ectopic Site , 2002, Current Biology.

[36]  S. Berger,et al.  Trans-tail histone modifications: wedge or bridge? , 2002, Nature Structural Biology.

[37]  D. Reinberg,et al.  Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. , 2002, Genes & development.

[38]  Kevin Struhl,et al.  Methylation of H3-Lysine 79 Is Mediated by a New Family of HMTases without a SET Domain , 2002, Current Biology.

[39]  Mark Johnston,et al.  Methylation of Histone H3 by COMPASS Requires Ubiquitination of Histone H2B by Rad6* , 2002, The Journal of Biological Chemistry.

[40]  S. Dhanasekaran,et al.  The polycomb group protein EZH2 is involved in progression of prostate cancer , 2002, Nature.

[41]  Hengbin Wang,et al.  Purification and Functional Characterization of SET8, a Nucleosomal Histone H4-Lysine 20-Specific Methyltransferase , 2002, Current Biology.

[42]  Andrew J. Bannister,et al.  Histone Methylation Dynamic or Static? , 2002, Cell.

[43]  Ira M. Hall,et al.  Establishment and Maintenance of a Heterochromatin Domain , 2002, Science.

[44]  H. Kato,et al.  G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. , 2002, Genes & development.

[45]  Kevin Struhl,et al.  Ubiquitination of Histone H2B by Rad6 Is Required for Efficient Dot1-mediated Methylation of Histone H3 Lysine 79* , 2002, The Journal of Biological Chemistry.

[46]  J. P. Jackson,et al.  Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase , 2002, Nature.

[47]  Philip R. Gafken,et al.  Dot1p Modulates Silencing in Yeast by Methylation of the Nucleosome Core , 2002, Cell.

[48]  Hengbin Wang,et al.  Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing , 2002, Science.

[49]  Ira M. Hall,et al.  Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi , 2002, Science.

[50]  Kevin Struhl,et al.  Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. , 2002, Genes & development.

[51]  J. Hansen,et al.  Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions. , 2002, Annual review of biophysics and biomolecular structure.

[52]  A. Bird DNA methylation patterns and epigenetic memory. , 2002, Genes & development.

[53]  Stuart L. Schreiber,et al.  Methylation of histone H3 Lys 4 in coding regions of active genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Brian D. Strahl,et al.  Gene silencing: Trans-histone regulatory pathway in chromatin , 2002, Nature.

[55]  Stuart L Schreiber,et al.  Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. , 2003, Molecular cell.

[56]  J. Min,et al.  Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. , 2003, Genes & development.

[57]  Hengbin Wang,et al.  Role of Histone H3 Lysine 27 Methylation in X Inactivation , 2003, Science.

[58]  G. Cagney,et al.  Methylation of Histone H3 by Set2 in Saccharomyces cerevisiae Is Linked to Transcriptional Elongation by RNA Polymerase II , 2003, Molecular and Cellular Biology.

[59]  J. Yates,et al.  The Set2 Histone Methyltransferase Functions through the Phosphorylated Carboxyl-terminal Domain of RNA Polymerase II* , 2003, The Journal of Biological Chemistry.

[60]  J. Martens,et al.  Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. , 2003, Molecular cell.

[61]  F. P. Villena,et al.  Genome imprinting regulated by the mouse Polycomb group protein Eed , 2003, Nature Genetics.

[62]  Yi Zhang,et al.  mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. , 2003, Molecular cell.

[63]  Ali Shilatifard,et al.  Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. , 2003, Genes & development.

[64]  Beatrix Ueberheide,et al.  Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. , 2003, Molecular cell.

[65]  K. Struhl,et al.  Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[66]  J. Herman,et al.  Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. , 2003, Cancer cell.

[67]  Kevin Struhl,et al.  Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. , 2003, Molecular cell.

[68]  N. Brockdorff,et al.  Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. , 2003, Developmental cell.

[69]  Michael Grunstein,et al.  Histone acetylation and deacetylation in yeast , 2003, Nature Reviews Molecular Cell Biology.

[70]  Youngchang Kim,et al.  Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. , 2003, Genes & development.

[71]  Christoph H Borchers,et al.  Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. , 2003, Genes & development.

[72]  En Li,et al.  Suv 39 h-Mediated Histone H 3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin , 2003 .

[73]  T. Jenuwein,et al.  An epigenetic road map for histone lysine methylation , 2003, Journal of Cell Science.

[74]  Yi Zhang,et al.  The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. , 2004, Current opinion in genetics & development.

[75]  T. Sugiyama,et al.  RITS acts in cis to promote RNA interference–mediated transcriptional and post-transcriptional silencing , 2004, Nature Genetics.

[76]  Charles Kooperberg,et al.  The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. , 2004, Genes & development.

[77]  S. Gygi,et al.  Two RNAi Complexes, RITS and RDRC, Physically Interact and Localize to Noncoding Centromeric RNAs , 2004, Cell.

[78]  Edith Heard,et al.  Recent advances in X-chromosome inactivation. , 2004, Current opinion in cell biology.

[79]  Steven Clarke,et al.  Human PAD4 Regulates Histone Arginine Methylation Levels via Demethylimination , 2004, Science.

[80]  Patrick England,et al.  Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3 , 2004, EMBO reports.

[81]  N. Krogan,et al.  Histone H 2 B Ubiquitylation Is Associated with Elongating RNA Polymerase II , 2004 .

[82]  Karl Henry,et al.  Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. , 2004, Genes & development.

[83]  M. Vidal,et al.  Role of histone H2A ubiquitination in Polycomb silencing , 2004, Nature.

[84]  Songtao Jia,et al.  RNAi-Mediated Targeting of Heterochromatin by the RITS Complex , 2004, Science.

[85]  N. Brockdorff,et al.  Reactivation of the Paternal X Chromosome in Early Mouse Embryos , 2004, Science.

[86]  A. Harel-Bellan,et al.  A Suv39h‐dependent mechanism for silencing S‐phase genes in differentiating but not in cycling cells , 2004, The EMBO journal.

[87]  T. Jenuwein,et al.  Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3 , 2004, The EMBO journal.

[88]  Shireen A. Sarraf,et al.  Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. , 2004, Molecular cell.

[89]  Yi Zhang,et al.  Hierarchical recruitment of polycomb group silencing complexes. , 2004, Molecular cell.

[90]  Yi Zhang,et al.  SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. , 2004, Molecular cell.

[91]  Paul Tempst,et al.  Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. , 2004, Molecular cell.

[92]  S. Grewal,et al.  Heterochromatin Regulates Cell Type-Specific Long-Range Chromatin Interactions Essential for Directed Recombination , 2004, Cell.

[93]  Haruhiko Koseki,et al.  Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. , 2004, Developmental cell.

[94]  Tom J. Petty,et al.  Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks , 2004, Nature.

[95]  K. Mitsuya,et al.  Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation , 2004, Nature Genetics.

[96]  J. Mata,et al.  Methylation of Histone H4 Lysine 20 Controls Recruitment of Crb2 to Sites of DNA Damage , 2004, Cell.

[97]  John R Yates,et al.  Deubiquitination of Histone H2B by a Yeast Acetyltransferase Complex Regulates Transcription* , 2004, Journal of Biological Chemistry.

[98]  E. Selker,et al.  HP1 is essential for DNA methylation in neurospora. , 2004, Molecular cell.

[99]  Danny Reinberg,et al.  A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. , 2004, Genes & development.

[100]  E. Ezhkova,et al.  Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. , 2004, Molecular cell.

[101]  Paul Tempst,et al.  Histone Deimination Antagonizes Arginine Methylation , 2004, Cell.

[102]  D. Reinberg,et al.  Epigenetic Dynamics of Imprinted X Inactivation During Early Mouse Development , 2004, Science.

[103]  Yang Shi,et al.  Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1 , 2004, Cell.

[104]  Yi Zhang,et al.  Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes , 2004, Nature Genetics.

[105]  W. Herr,et al.  A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. , 2004, Molecular cell.

[106]  Kristian Helin,et al.  Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity , 2004, The EMBO journal.

[107]  E. Li,et al.  Ring1b-mediated H2A Ubiquitination Associates with Inactive X Chromosomes and Is Involved in Initiation of X Inactivation* , 2004, Journal of Biological Chemistry.

[108]  T. Sugiyama,et al.  RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[109]  Tsutomu Ohta,et al.  Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. , 2005, Genes & development.

[110]  Eric S. Lander,et al.  Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse , 2005, Cell.

[111]  N. Krogan,et al.  Histone H2B Ubiquitylation Is Associated with Elongating RNA Polymerase II , 2005, Molecular and Cellular Biology.

[112]  R. Allshire,et al.  Methylation: lost in hydroxylation? , 2005, EMBO reports.

[113]  D. Reinberg,et al.  The key to development: interpreting the histone code? , 2005, Current opinion in genetics & development.

[114]  Yi Zhang,et al.  hDOT1L Links Histone Methylation to Leukemogenesis , 2005, Cell.

[115]  John R. Yates,et al.  Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation , 2005, Nature.

[116]  Thomas A. Milne,et al.  Physical Association and Coordinate Function of the H3 K4 Methyltransferase MLL1 and the H4 K16 Acetyltransferase MOF , 2005, Cell.

[117]  G. Blobel,et al.  Histone H3 Lysine 9 Methylation and HP1γ Are Associated with Transcription Elongation through Mammalian Chromatin. , 2005 .

[118]  Mark T Bedford,et al.  Arginine methylation an emerging regulator of protein function. , 2005, Molecular cell.

[119]  Antoine H. F. M. Peters,et al.  LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription , 2005, Nature.

[120]  Bradley R Cairns,et al.  Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains , 2005, The EMBO journal.

[121]  Min Gyu Lee,et al.  An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation , 2005, Nature.

[122]  R. Paro,et al.  Intergenic transcription through a polycomb group response element counteracts silencing. , 2005, Genes & development.

[123]  Steven Henikoff,et al.  Histone modifications: combinatorial complexity or cumulative simplicity? , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[124]  Làszlò Tora,et al.  SAGA unveiled. , 2005, Trends in biochemical sciences.

[125]  Geoff Kelly,et al.  Specificity and mechanism of the histone methyltransferase Pr-Set7. , 2005, Genes & development.

[126]  T. Hughes,et al.  BUR Kinase Selectively Regulates H3 K4 Trimethylation and H2B Ubiquitylation through Recruitment of the PAF Elongation Complex , 2005, Current Biology.

[127]  Thomas A. Milne,et al.  WDR5 Associates with Histone H3 Methylated at K4 and Is Essential for H3 K4 Methylation and Vertebrate Development , 2005, Cell.

[128]  Stormy J. Chamberlain,et al.  The Murine Polycomb Group Protein Eed Is Required for Global Histone H3 Lysine-27 Methylation , 2005, Current Biology.

[129]  R. Allshire,et al.  The role of heterochromatin in centromere function , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[130]  Megan F. Cole,et al.  Genome-wide Map of Nucleosome Acetylation and Methylation in Yeast , 2005, Cell.

[131]  Tony Kouzarides,et al.  Reversing histone methylation , 2005, Nature.

[132]  D. Reinberg,et al.  PR-Set7-dependent methylation of histone H4 Lys 20 functions in repression of gene expression and is essential for mitosis. , 2005, Genes & development.