Histone Ubiquitylation and the Regulation of Transcription

  • Mary Ann Osley
  • Alastair B. Fleming
  • Cheng-Fu Kao
Chapter
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 41)

Abstract

The small (76 amino acids) and highly conserved ubiquitin protein plays key roles in the physiology of eukaryotic cells. Protein ubiquitylation has emerged as one of the most important intracellular signaling mechanisms, and in 2004 the Nobel Prize was awarded to Aaron Ciechanower, Avram Hersko, and Irwin Rose for their pioneering studies of the enzymology of ubiquitin attachment. One of the most common features of protein ubiquitylation is the attachment of polyubiquitin chains (four or more ubiquitin moieties attached to each other), which is a widely used mechanism to target proteins for degradation via the 26S proteosome. However, it is noteworthy that the first ubiquitylated protein to be identified was histone H2A, to which a single ubiquitin moiety is most commonly attached. Following this discovery, other histones (H2B, H3, H1, H2A.Z, macroH2A), as well as many nonhistone proteins, have been found to be monoubiquitylated. The role of monoubiquitylation is still elusive because a single ubiquitin moiety is not sufficient to target proteins for turnover, and has been hypothesized to control the assembly or disassembly of multiprotein complexes by providing a protein-binding site. Indeed, a number of ubiquitin-binding domains have now been identified in both polyubiquitylated and monoubiquitylated proteins. Despite the early discovery of ubiquitylated histones, it has only been in the last five or so years that we have begun to understand how histone ubiquitylation is regulated and what roles it plays in the cell. This review will discuss current research on the factors that regulate the attachment and removal of ubiquitin from histones, describe the relationship of histone ubiquitylation to histone methylation, and focus on the roles of ubiquitylated histones in gene expression.

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Notes

Acknowledgments

The authors thank Shelley Berger, Danny Reinberg, and Yi Zhao for generously sharing unpublished data. Work from the authors' laboratory is supported by a grant from the NIH (GM40118) to M.A.O. and a Leukemia and Lymphoma Society Special Fellow award to C.-F.K.

References

  1. 1.
    Amar N, Messenguy F et al. (2000) ArgrII, a component of the Argr-Mcm1 complex involved in the control of arginine metabolism in Saccharomyces cerevisiae, is the sensor of arginine. Mol Cell Biol 20:2087–2097 PubMedCrossRefGoogle Scholar
  2. 2.
    Amerik AY, Li SJ et al. (2000) Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae. Biol Chem 381:981–992 PubMedCrossRefGoogle Scholar
  3. 3.
    Baarends WM, Hoogerbrugge JW et al. (1999) Histone ubiquitination and chromatin remodeling in mouse spermatogenesis. Dev Biol 207:322–333 PubMedCrossRefGoogle Scholar
  4. 4.
    Baarends WM, Wassenaar E et al. (2005) Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Mol Cell Biol 25:1041–1053 PubMedCrossRefGoogle Scholar
  5. 5.
    Bailly V, Lauder S et al. (1997) Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J Biol Chem 272:23 360–23 365 Google Scholar
  6. 6.
    Ballal NR, Kang YJ et al. (1975) Changes in nucleolar proteins and their phosphorylation patterns during liver regeneration. J Biol Chem 250:5921–5925 PubMedGoogle Scholar
  7. 7.
    Bannister AJ, Schneider R et al. (2005) Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J Biol Chem 280:17 732–17 736 Google Scholar
  8. 8.
    Barsoum J, Varshavsky A (1985) Preferential localization of variant nucleosomes near the 5′-end of the mouse dihydrofolate reductase gene. J Biol Chem 260:7688–7697 PubMedGoogle Scholar
  9. 9.
    Bartel B, Wunning I et al. (1990) The recognition component of the n-end rule pathway. EMBO J 9:3179–3189 PubMedGoogle Scholar
  10. 10.
    Bernstein BE, Humphrey EL et al. (2002) Methylation of histone H3 Lys 4 in coding regions of active genes. Proc Natl Acad Sci USA 99:8695–8700 PubMedCrossRefGoogle Scholar
  11. 11.
    Bhaumik SR, Green MR (2002) Differential requirement of SAGA components for recruitment of TATA-box-binding protein to promoters in vivo. Mol Cell Biol 22:7365–7371 PubMedCrossRefGoogle Scholar
  12. 12.
    Bohm L, Crane-Robinson C et al. (1980) Proteolytic digestion studies of chromatin core-histone structure. Identification of a limit peptide of histone H2A. Eur J Biochem 106:525–530 PubMedCrossRefGoogle Scholar
  13. 13.
    Bray S, Musisi H et al. (2005) Bre1 is required for notch signaling and histone modification. Dev Cell 8:279–286 PubMedCrossRefGoogle Scholar
  14. 14.
    Briggs SD, Xiao T et al. (2002) Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418:498 PubMedCrossRefGoogle Scholar
  15. 15.
    Broomfield S, Hryciw T et al. (2001) DNA postreplication repair and mutagenesis in Saccharomyces cerevisiae. Mutat Res 486:167–184 PubMedGoogle Scholar
  16. 16.
    Bryk M, Briggs SD et al. (2002) Evidence that Set1, a factor required for methylation of histone H3, regulates rDna silencing in S. cerevisiae by a Sir2-independent mechanism. Curr Biol 12:165–170 PubMedCrossRefGoogle Scholar
  17. 17.
    Buchberger A (2002) From Uba to Ubx: new words in the ubiquitin vocabulary. Trends Cell Biol 12:216–221 PubMedCrossRefGoogle Scholar
  18. 18.
    Cai SY, Babbitt RW et al. (1999) A mutant deubiquitinating enzyme (Ubp-m) associates with mitotic chromosomes and blocks cell division. Proc Natl Acad Sci USA 96:2828–2833 PubMedCrossRefGoogle Scholar
  19. 19.
    Cao R, Tsukuda YI, Zhang Y (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20:845–854 PubMedCrossRefGoogle Scholar
  20. 20.
    Cao R, Wang L et al. (2002) Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science 298:1039–1043 PubMedCrossRefGoogle Scholar
  21. 21.
    Carvin CD, Kladde MP (2004) Effectors of lysine 4 methylation of histone H3 in Saccharomyces cerevisiae are negative regulators of Pho5 and Gal1-10. J Biol Chem 279:33 057–33 062 CrossRefGoogle Scholar
  22. 22.
    Chadwick BP, Willard HF (2003) Chromatin of the barr body: histone and non-histone proteins associated with or excluded from the inactive X chromosome. Hum Mol Genet 12:2167–2178 PubMedCrossRefGoogle Scholar
  23. 23.
    Chang M, French-Cornay D et al. (1999) A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol 19:1056–1067 PubMedGoogle Scholar
  24. 24.
    Chen HY, Sun JM et al. (1998) Ubiquitination of histone H3 in elongating spermatids of rat testes. J Biol Chem 273:13 165–13 169 PubMedCrossRefGoogle Scholar
  25. 25.
    Cismowski MJ, Laff GM et al. (1995) Kin28 encodes a C-terminal domain kinase that controls mRNA transcription in Saccharomyces cerevisiae but lacks cyclin-dependent kinase-activating kinase (CAK) activity. Mol Cell Biol 15:2983–2992 PubMedGoogle Scholar
  26. 26.
    Citterio E, Papait R et al. (2004) Np95 is a histone-binding protein endowed with ubiquitin ligase activity. Mol Cell Biol 24:2526–2535 PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen HR, Royce-Tolland ME et al. (2005) Chromatin modifications on the inactive X chromosome. Prog Mol Subcell Biol 38:91–122 PubMedGoogle Scholar
  28. 28.
    Costa PJ, Arndt KM (2000) Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae Rtf1 protein in transcription elongation. Genetics 156:535–547 Google Scholar
  29. 29.
    Daniel JA, Torok MS et al. (2004) Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription. J Biol Chem 279:1867–1871 PubMedCrossRefGoogle Scholar
  30. 30.
    Davie JR, Lin R et al. (1991) Timing of the appearance of ubiquitinated histones in developing new macronuclei of Tetrahymena thermophila. Biochem Cell Biol 69:66–71 Google Scholar
  31. 31.
    Davies N, Lindsey GG (1994) Histone H2B (and H2A) ubiquitination allows normal histone octamer and core particle reconstitution. Biochim Biophys Acta 1218:187–193 PubMedGoogle Scholar
  32. 32.
    de Napoles M, Mermoud JE et al. (2004) Polycomb group proteins Ring1a/b link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell 7:663–676 PubMedCrossRefGoogle Scholar
  33. 33.
    Dejardin J, Cavalli G (2005) Epigenetic inheritance of chromatin states mediated by Polycomb and Trithorax group proteins in Drosophila. Prog Mol Subcell Biol 38:31–63 PubMedGoogle Scholar
  34. 34.
    Dong L, Xu CW (2004) Carbohydrates induce mono-ubiquitination of H2B in yeast. J Biol Chem 279:1577–1580 PubMedCrossRefGoogle Scholar
  35. 35.
    Dor Y, Raboy B et al. (1996) Role of the conserved carboxy-terminal alpha-helix of Rad6p in ubiquitination and DNA repair. Mol Microbiol 21:1197–1206 PubMedCrossRefGoogle Scholar
  36. 36.
    Dou Y, Milne TA et al. (2005) Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase mof. Cell 121:873–885 Google Scholar
  37. 37.
    Dover J, Schneider J et al. (2002) Methylation of histone H3 by compass requires ubiquitination of histone H2B by Rad6. J Biol Chem 277:28 368–28 371 CrossRefGoogle Scholar
  38. 38.
    Dudley AM, Rougeulle C et al. (1999) The Spt components of SAGA facilitate TBP binding to a promoter at a post-activator-binding step in vivo. Genes Dev 13:2940–2945 PubMedCrossRefGoogle Scholar
  39. 39.
    Emre NC, Berger SL (2004) Histone H2B ubiquitylation and deubiquitylation in genomic regulation. Cold Spring Harb Symp Quant Biol 69:289–299 PubMedCrossRefGoogle Scholar
  40. 40.
    Emre NC, Ingvarsdottir K et al. (2005) Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing. Mol Cell 17:585–594 PubMedCrossRefGoogle Scholar
  41. 41.
    Ezhkova E, Tansey WP (2004) Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. Mol Cell 13:435–442 PubMedCrossRefGoogle Scholar
  42. 42.
    Fang J, Chen T et al. (2004) Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is involved in initiation of X inactivation. J Biol Chem 279:52 812–52 815 Google Scholar
  43. 43.
    Fischle W, Wang Y et al. (2003) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183 PubMedCrossRefGoogle Scholar
  44. 44.
    Francis NJ, Kingston RE et al. (2004) Chromatin compaction by a Polycomb group protein complex. Science 306:1574–1577 PubMedCrossRefGoogle Scholar
  45. 45.
    Francis NJ, Saurin AJ et al. (2001) Reconstitution of a functional core Polycomb repressive complex. Mol Cell 8:545–556 PubMedCrossRefGoogle Scholar
  46. 46.
    Game JC, Williamson MS et al. (2005) X-ray survival characteristics and genetic analysis for nine Saccharomyces deletion mutants that show altered radiation sensitivity. Genetics 169:51–63 CrossRefGoogle Scholar
  47. 47.
    Gardner RG, Nelson ZW et al. (2005) Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: distinct roles in telomeric silencing and general chromatin. Mol Cell Biol 25:6123–6139 PubMedCrossRefGoogle Scholar
  48. 48.
    Gerber M, Shilatifard A (2003) Transcriptional elongation by RNA polymerase II and histone methylation. J Biol Chem 278:26 303–26 306 CrossRefGoogle Scholar
  49. 49.
    Giannattasio M, Lazzaro F et al. (2005) The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem 280:9879–9886 PubMedCrossRefGoogle Scholar
  50. 50.
    Goldknopf IL, Busch H (1977) Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proc Natl Acad Sci USA 74:864–868 PubMedGoogle Scholar
  51. 51.
    Goldknopf IL, French MF et al. (1978) A reciprocal relationship between contents of free ubiquitin and protein A24, its conjugate with histone 2A, in chromatin fractions obtained by the DNase II, Mg++ procedure. Biochem Biophys Res Commun 84:786–793 PubMedCrossRefGoogle Scholar
  52. 52.
    Goldknopf IL, Sudhakar S et al. (1980) Timing of ubiquitin synthesis and conjugation into protein A24 during the Hela cell cycle. Biochem Biophys Res Commun 95:1253–1260 PubMedCrossRefGoogle Scholar
  53. 53.
    Goldknopf IL, Taylor CW et al. (1975) Isolation and characterization of protein A24, a histone-like non-histone chromosomal protein. J Biol Chem 250:7182–7187 PubMedGoogle Scholar
  54. 54.
    Greer SF, Zika E et al. (2003) Enhancement of CIITA transcriptional function by ubiquitin. Nat Immunol 4:1074–1082 PubMedCrossRefGoogle Scholar
  55. 55.
    Haglund K, Di Fiore PP et al. (2003) Distinct monoubiquitin signals in receptor endocytosis. Trends Biochem Sci 28:598–603 PubMedCrossRefGoogle Scholar
  56. 56.
    Hanson RD, Hess JL et al. (1999) Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development. Proc Natl Acad Sci USA 96:14 372–14 377 CrossRefGoogle Scholar
  57. 57.
    Henry KW, Berger SL (2002) Trans-tail histone modifications: wedge or bridge? Nat Struct Biol 9:565–566 PubMedCrossRefGoogle Scholar
  58. 58.
    Henry KW, Wyce A et al. (2003) Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev 17:2648–2663 PubMedCrossRefGoogle Scholar
  59. 59.
    Hernandez-Munoz I, Lund AH et al. (2005) Stable X chromosome inactivation involves the PRC1 polycomb complex and requires histone macroH2A1 and the Cullin3/Spop ubiquitin E3 ligase. Proc Natl Acad Sci USA 102:7635–7640 PubMedCrossRefGoogle Scholar
  60. 60.
    Hicke L (2001) Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol 2:195–201 PubMedCrossRefGoogle Scholar
  61. 61.
    Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172 PubMedCrossRefGoogle Scholar
  62. 62.
    Hochstrasser M (1995) Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol 7:215–223 PubMedCrossRefGoogle Scholar
  63. 63.
    Hoege C, Pfander B et al. (2002) Rad6-dependent DNA repair is linked to modification of PCNA by ubiquitin and sumo. Nature 419:135–141 PubMedCrossRefGoogle Scholar
  64. 64.
    Huang H, Kahana A et al. (1997) The ubiquitin-conjugating enzyme Rad6 (Ubc2) is required for silencing in Saccharomyces cerevisiae. Mol Cell Biol 17:6693–6699 PubMedGoogle Scholar
  65. 65.
    Huyen Y, Zgheib O et al. (2004) Methylated lysine 79 of histone H3 targets 53bp1 to DNA double-strand breaks. Nature 432:406–411 PubMedCrossRefGoogle Scholar
  66. 66.
    Hwang WW, Venkatasubrahmanyam S et al. (2003) A conserved ring finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell 11:261–266 PubMedCrossRefGoogle Scholar
  67. 67.
    Ingvarsdottir K, Krogan NJ et al. (2005) H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex. Mol Cell Biol 25:1162–1172 PubMedCrossRefGoogle Scholar
  68. 68.
    Jaenisch R, Beard C et al. (1998) Mammalian X chromosome inactivation. Novartis Found Symp 214:200–209; discussion 209–213, 228–232 PubMedGoogle Scholar
  69. 69.
    Jason LJ, Finn RM et al. (2005) Histone H2A ubiquitination does not preclude histone H1 binding, but it facilitates its association with the nucleosome. J Biol Chem 280:4975–4982 PubMedCrossRefGoogle Scholar
  70. 70.
    Jason LJ, Moore SC et al. (2001) Magnesium-dependent association and folding of oligonucleosomes reconstituted with ubiquitinated H2A. J Biol Chem 276:14597–14601 PubMedCrossRefGoogle Scholar
  71. 71.
    Jason LJ, Moore SC et al. (2002) Histone ubiquitination: a tagging tail unfolds? Bioessays 24:166–174 PubMedCrossRefGoogle Scholar
  72. 72.
    Jentsch S, McGrath JP et al. (1987) The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329:131–134 PubMedCrossRefGoogle Scholar
  73. 73.
    Joazeiro CA, Weissman AM (2000) Ring finger proteins: mediators of ubiquitin ligase activity. Cell 102:549–552 PubMedCrossRefGoogle Scholar
  74. 74.
    Kang RS, Daniels CM et al. (2003) Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding. Cell 113:621–630 PubMedCrossRefGoogle Scholar
  75. 75.
    Kao CF, Hillyer C et al. (2004) Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev 18:184–195 PubMedCrossRefGoogle Scholar
  76. 76.
    Kaplan CD, Holland MJ et al. (2005) Interaction between transcription elongation factors and mRNA 3′-end formation at the Saccharomyces cerevisiae GAL10-GAL7 locus. J Biol Chem 280:913–922 PubMedCrossRefGoogle Scholar
  77. 77.
    Koken M, Reynolds P et al. (1991) Dhr6, a Drosophila homolog of the yeast DNA-repair gene RAD6. Proc Natl Acad Sci USA 88:3832–3836 PubMedGoogle Scholar
  78. 78.
    Koken MH, Hoogerbrugge JW et al. (1996) Expression of the ubiquitin-conjugating DNA repair enzymes hHR6a and b suggests a role in spermatogenesis and chromatin modification. Dev Biol 173:119–132 PubMedCrossRefGoogle Scholar
  79. 79.
    Koken MH, Reynolds P et al. (1991) Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6. Proc Natl Acad Sci USA 88:8865–8869 PubMedGoogle Scholar
  80. 80.
    Kouzarides T (2002) Histone methylation in transcriptional control. Curr Opin Genet Dev 12:198–209 PubMedCrossRefGoogle Scholar
  81. 81.
    Krogan NJ, Dover J et al. (2003) The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell 11:721–729 PubMedCrossRefGoogle Scholar
  82. 82.
    Krogan NJ, Kim M et al. (2002) RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. Mol Cell Biol 22:6979–6992 PubMedCrossRefGoogle Scholar
  83. 83.
    Krogan NJ, Kim M et al. (2003) Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol 23:4207–4218 PubMedCrossRefGoogle Scholar
  84. 84.
    Laribee RN, Krogan NJ et al. (2005) BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex. Curr Biol 15:1487–1493 PubMedCrossRefGoogle Scholar
  85. 85.
    Larschan E, Winston F (2001) The S. cerevisiae SAGA complex functions in vivo as a coactivator for transcriptional activation by Gal4. Genes Dev 15:1946–1956 PubMedCrossRefGoogle Scholar
  86. 86.
    Larschan E, Winston F (2005) The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Mol Cell Biol 25:114–123 PubMedCrossRefGoogle Scholar
  87. 87.
    Lee KK, Florens L et al. (2005) The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex. Mol Cell Biol 25:1173–1182 PubMedCrossRefGoogle Scholar
  88. 88.
    Levinger L, Varshavsky A (1982) Selective arrangement of ubiquitinated and d1 protein-containing nucleosomes within the Drosophila genome. Cell 28:375–385 PubMedCrossRefGoogle Scholar
  89. 89.
    Lo WS, Henry KW et al. (2004) Histone modification patterns during gene activation. Methods Enzymol 377:130–153 PubMedCrossRefGoogle Scholar
  90. 90.
    Milne TA, Briggs SD et al. (2002) MLL targets set domain methyltransferase activity to Hox gene promoters. Mol Cell 10:1107–1117 PubMedCrossRefGoogle Scholar
  91. 91.
    Mimnaugh EG, Kayastha G et al. (2001) Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli. Cell Death Differ 8:1182–1196 Google Scholar
  92. 92.
    Minsky N, Oren M (2004) The ring domain of Mdm2 mediates histone ubiquitylation and transcriptional repression. Mol Cell 16:631–639 PubMedCrossRefGoogle Scholar
  93. 93.
    Montelone BA, Prakash S et al. (1981) Recombination and mutagenesis in rad6 mutants of Saccharomyces cerevisiae: evidence for multiple functions of the RAD6 gene. Mol Gen Genet 184:410–415 PubMedCrossRefGoogle Scholar
  94. 94.
    Moore SC, Jason L et al. (2002) The elusive structural role of ubiquitinated histones. Biochem Cell Biol 80:311–319 Google Scholar
  95. 95.
    Morrison A, Miller EJ et al. (1988) Domain structure and functional analysis of the carboxyl-terminal polyacidic sequence of the Rad6 protein of Saccharomyces cerevisiae. Mol Cell Biol 8:1179–1185 PubMedGoogle Scholar
  96. 96.
    Mueller RD, Yasuda H et al. (1985) Identification of ubiquitinated histones 2A and 2B in Physarum polycephalum. Disappearance of these proteins at metaphase and reappearance at anaphase. J Biol Chem 260:5147–5153 PubMedGoogle Scholar
  97. 97.
    Mueller TD, Feigon J (2002) Solution structures of UBA domains reveal a conserved hydrophobic surface for protein–protein interactions. J Mol Biol 319:1243–1255 PubMedCrossRefGoogle Scholar
  98. 98.
    Muller J, Hart CM et al. (2002) Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111:197–208 PubMedCrossRefGoogle Scholar
  99. 99.
    Ng HH, Ciccone DN et al. (2003) Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. Proc Natl Acad Sci USA 100:1820–1825 PubMedCrossRefGoogle Scholar
  100. 100.
    Ng HH, Dole S et al. (2003) The Rtf1 component of the PAF1 transcriptional elongation complex is required for ubiquitination of histone H2B. J Biol Chem 278:33 625–33 628 Google Scholar
  101. 101.
    Ng HH, Feng Q et al. (2002) Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev 16:1518–1527 PubMedCrossRefGoogle Scholar
  102. 102.
    Ng HH, Robert F et al. (2003) Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 11:709–719 PubMedCrossRefGoogle Scholar
  103. 103.
    Ng HH, Xu RM et al. (2002) Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J Biol Chem 277:34 655–34 657 Google Scholar
  104. 104.
    Nickel BE, Allis CD et al. (1989) Ubiquitinated histone H2B is preferentially located in transcriptionally active chromatin. Biochemistry 28:958–963 PubMedCrossRefGoogle Scholar
  105. 105.
    Nickel BE, Roth SY et al. (1987) Changes in the histone H2A variant H2A.Z and polyubiquitinated histone species in developing trout testis. Biochemistry 26:4417–4421 PubMedCrossRefGoogle Scholar
  106. 106.
    Nislow C, Ray E et al. (1997) Set1, a yeast member of the Trithorax family, functions in transcriptional silencing and diverse cellular processes. Mol Biol Cell 8:2421–2436 PubMedGoogle Scholar
  107. 107.
    O'Brien T, Tjian R (2000) Different functional domains of TAFII250 modulate expression of distinct subsets of mammalian genes. Proc Natl Acad Sci USA 97:2456–2461 PubMedCrossRefGoogle Scholar
  108. 108.
    Oh S, Zhang H et al. (2004) A mechanism related to the yeast transcriptional regulator PAF1c is required for expression of the Arabidopsis Flc/Maf Mads box gene family. Plant Cell 16:2940–2953 PubMedCrossRefGoogle Scholar
  109. 109.
    Orlandi I, Bettiga M et al. (2004) Transcriptional profiling of ubp10 null mutant reveals altered subtelomeric gene expression and insurgence of oxidative stress response. J Biol Chem 279:6414–6425 PubMedCrossRefGoogle Scholar
  110. 110.
    Orphanides G, Reinberg D (2000) Rna polymerase II elongation through chromatin. Nature 407:471–475 PubMedCrossRefGoogle Scholar
  111. 111.
    Pham AD, Sauer F (2000) Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation of gene expression in Drosophila. Science 289:2357–2360 PubMedCrossRefGoogle Scholar
  112. 112.
    Pickart CM (1997) Targeting of substrates to the 26s proteasome. Faseb J 11:1055–1066 PubMedGoogle Scholar
  113. 113.
    Pickart CM (2001a) Mechanisms underlying ubiquitination. Annu Rev Biochem 70:503–533 Google Scholar
  114. 114.
    Pickart CM (2001b) Ubiquitin enters the new millennium. Mol Cell 8:499–504 Google Scholar
  115. 115.
    Pickart CM, Eddins MJ (2004) Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta 1695:55–72 PubMedCrossRefGoogle Scholar
  116. 116.
    Plath K, Fang J et al. (2003) Role of histone H3 lysine 27 methylation in X inactivation. Science 300:131–135 PubMedCrossRefGoogle Scholar
  117. 117.
    Pokholok DK, Hannett NM et al. (2002) Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9:799–809 PubMedCrossRefGoogle Scholar
  118. 118.
    Pokholok DK, Harbison CT et al. (2005) Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122:517–527 Google Scholar
  119. 119.
    Polo S, Sigismund S et al. (2002) A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature 416:451–455 PubMedCrossRefGoogle Scholar
  120. 120.
    Powell DW, Weaver CM et al. (2004) Cluster analysis of mass spectrometry data reveals a novel component of SAGA. Mol Cell Biol 24:7249–7259 PubMedCrossRefGoogle Scholar
  121. 121.
    Prag G, Misra S et al. (2003) Mechanism of ubiquitin recognition by the CUE domain of Vps9p. Cell 113:609–620 PubMedCrossRefGoogle Scholar
  122. 122.
    Prakash L (1981) Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Mol Gen Genet 184:471–478 PubMedCrossRefGoogle Scholar
  123. 123.
    Pray-Grant MG, Daniel JA et al. (2005) Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433:434–438 PubMedCrossRefGoogle Scholar
  124. 124.
    Raasi S, Pickart CM (2005) Ubiquitin chain synthesis. Methods Mol Biol 301:47–55 PubMedGoogle Scholar
  125. 125.
    Raboy B, Kulka RG (1994) Role of the C-terminus of Saccharomyces cerevisiae ubiquitin-conjugating enzyme (Rad6) in substrate and ubiquitin-protein-ligase (E3-r) interactions. Eur J Biochem 221:247–251 PubMedCrossRefGoogle Scholar
  126. 126.
    Rao B, Shibata Y, Strahl B, Lieb JD (2005) Dimethylation of histone H3 at lysine 30 demarcates regulatory and nonregulatory chromatin genome-wide. Mol Cell Biol 25:9447–9459 PubMedCrossRefGoogle Scholar
  127. 127.
    Reverol L, Chirinos M et al. (1997) Presence of an unusually high concentration of an ubiquitinated histone-like protein in Trypanosoma cruzi. J Cell Biochem 66:433–440 PubMedCrossRefGoogle Scholar
  128. 128.
    Reynolds P, Koken MH et al. (1990) The rhp6+ gene of Schizosaccharomyces pombe: a structural and functional homolog of the RAD6 gene from the distantly related yeast Saccharomyces cerevisiae. EMBO J 9:1423–1430 PubMedGoogle Scholar
  129. 129.
    Ricci AR, Genereaux J et al. (2002) Components of the SAGA histone acetyltransferase complex are required for repressed transcription of ARG1 in rich medium. Mol Cell Biol 22:4033–4042 PubMedCrossRefGoogle Scholar
  130. 130.
    Robzyk K, Recht J et al. (2000) RAD6-dependent ubiquitination of histone H2B in yeast. Science 287:501–504 PubMedCrossRefGoogle Scholar
  131. 131.
    Roest HP, Baarends WM et al. (2004) The ubiquitin-conjugating DNA repair enzyme HR6A is a maternal factor essential for early embryonic development in mice. Mol Cell Biol 24:5485–5495 PubMedCrossRefGoogle Scholar
  132. 132.
    Roest HP, van Klaveren J et al. (1996) Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell 86:799–810 PubMedCrossRefGoogle Scholar
  133. 133.
    Ruppert S, Wang EH et al. (1993) Cloning and expression of human TAFII250: a TBP-associated factor implicated in cell-cycle regulation. Nature 362:175–179 PubMedCrossRefGoogle Scholar
  134. 134.
    Rusche LN, Kirchmaier AL et al. (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem 72:481–516 PubMedCrossRefGoogle Scholar
  135. 135.
    San-Segundo PA, Roeder GS (2000) Role for the silencing protein Dot1 in meiotic checkpoint control. Mol Biol Cell 11:3601–3615 PubMedGoogle Scholar
  136. 136.
    Santos-Rosa H, Schneider R et al. (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419:407–411 PubMedCrossRefGoogle Scholar
  137. 137.
    Schneider J, Wood A et al. (2005) Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression. Mol Cell 19:849–856 PubMedCrossRefGoogle Scholar
  138. 138.
    Seale RL (1981) Rapid turnover of the histone–ubiquitin conjugate, protein A24. Nucleic Acids Res 9:3151–3158 PubMedGoogle Scholar
  139. 139.
    Shahbazian MD, Zhang K et al. (2005) Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Mol Cell 19:271–277 PubMedCrossRefGoogle Scholar
  140. 140.
    Shi X, Chang M et al. (1997) Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme. Mol Cell Biol 17:1160–1169 PubMedGoogle Scholar
  141. 141.
    Shi X, Finkelstein A et al. (1996) Paf1p, an RNA polymerase II-associated factor in Saccharomyces cerevisiae, may have both positive and negative roles in transcription. Mol Cell Biol 16:669–676 PubMedGoogle Scholar
  142. 142.
    Shih SC, Prag G et al. (2003) A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain. EMBO J 22:1273–1281 PubMedCrossRefGoogle Scholar
  143. 143.
    Sigismund S, Polo S et al. (2004) Signaling through monoubiquitination. Curr Top Microbiol Immunol 286:149–185 PubMedGoogle Scholar
  144. 144.
    Simic R, Lindstrom DL et al. (2003) Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes. EMBO J 22:1846–1856 PubMedCrossRefGoogle Scholar
  145. 145.
    Singh J, Goel V et al. (1998) A novel function of the DNA repair gene rhp6 in mating-type silencing by chromatin remodeling in fission yeast. Mol Cell Biol 18:5511–5522 PubMedGoogle Scholar
  146. 146.
    Smith KP, Byron M et al. (2004) Ubiquitinated proteins including uH2A on the human and mouse inactive X chromosome: enrichment in gene rich bands. Chromosoma 113:324–335 PubMedCrossRefGoogle Scholar
  147. 147.
    Sollier J, Lin W et al. (2004) SET1 is required for meiotic s-phase onset, double-strand break formation and middle gene expression. EMBO J 23:1957–1967 PubMedCrossRefGoogle Scholar
  148. 148.
    Squazzo SL, Costa PJ et al. (2002) The PAF1 complex physically and functionally associates with transcription elongation factors in vivo. EMBO J 21:1764–1774 PubMedCrossRefGoogle Scholar
  149. 149.
    Stelter P, Ulrich HD (2003) Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425:188–191 PubMedCrossRefGoogle Scholar
  150. 150.
    Sterner DE, Grant PA et al. (1999) Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TATA–binding protein interaction. Mol Cell Biol 19:86–98 PubMedGoogle Scholar
  151. 151.
    Sun ZW, Allis CD (2002) Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418:104–108 PubMedCrossRefGoogle Scholar
  152. 152.
    Sung P, Prakash S et al. (1988) The Rad6 protein of Saccharomyces cerevisiae polyubiquitinates histones, and its acidic domain mediates this activity. Genes Dev 2:1476–1485 PubMedGoogle Scholar
  153. 153.
    Sung P, Prakash S et al. (1990) Mutation of cysteine-88 in the Saccharomyces cerevisiae RAD6 protein abolishes its ubiquitin-conjugating activity and its various biological functions. Proc Natl Acad Sci USA 87:2695–2699 PubMedGoogle Scholar
  154. 154.
    Swerdlow PS, Schuster T et al. (1990) A conserved sequence in histone H2A which is a ubiquitination site in higher eucaryotes is not required for growth in Saccharomyces cerevisiae. Mol Cell Biol 10:4905–4911 PubMedGoogle Scholar
  155. 155.
    Tasaki T, Mulder LC et al. (2005) A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. Mol Cell Biol 25:7120–7136 PubMedCrossRefGoogle Scholar
  156. 156.
    Thorne AW, Sautiere P et al. (1987) The structure of ubiquitinated histone H2B. EMBO J 6:1005–1010 PubMedGoogle Scholar
  157. 157.
    Turner SD, Ricci AR et al. (2002) The E2 ubiquitin conjugase rad6 is required for the ArgR/Mcm1 repression of ARG1 transcription. Mol Cell Biol 22:4011–4019 PubMedCrossRefGoogle Scholar
  158. 158.
    Ulrich HD (2004) How to activate a damage-tolerant polymerase: consequences of PCNA modifications by ubiquitin and SUMO. Cell Cycle 3:15–18 PubMedGoogle Scholar
  159. 159.
    Ulrich HD, Jentsch S (2000) Two ring finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 19:3388–3397 PubMedCrossRefGoogle Scholar
  160. 160.
    van der Knaap JA, Kumar BR et al. (2005) Gmp synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer Usp7. Mol Cell 17:695–707 PubMedCrossRefGoogle Scholar
  161. 161.
    van Leeuwen F, Gafken PR et al. (2002) Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109:745–756 PubMedCrossRefGoogle Scholar
  162. 162.
    van Leeuwen F, Gottschling DE (2002) Genome-wide histone modifications: gaining specificity by preventing promiscuity. Curr Opin Cell Biol 14:756–762 PubMedCrossRefGoogle Scholar
  163. 163.
    Vassilev AP, Rasmussen HH et al. (1995) The levels of ubiquitinated histone H2A are highly upregulated in transformed human cells: partial colocalization of uH2A clusters and PCNA/cyclin foci in a fraction of cells in S-phase. J Cell Sci 108 (Part 3):1205–1215 Google Scholar
  164. 164.
    Wang H, Wang L et al. (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873–878 PubMedCrossRefGoogle Scholar
  165. 165.
    Wang L, Brown JL et al. (2004) Hierarchical recruitment of Polycomb group silencing complexes. Mol Cell 14:637–646 PubMedCrossRefGoogle Scholar
  166. 166.
    Watkins JF, Sung P et al. (1993) The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation. Genes Dev 7:250–261 PubMedGoogle Scholar
  167. 167.
    West MH, Bonner WM (1980) Histone 2B can be modified by the attachment of ubiquitin. Nucleic Acids Res 8:4671–4680 PubMedGoogle Scholar
  168. 168.
    Wilkinson KD (1997) Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. Faseb J 11:1245–1256 PubMedGoogle Scholar
  169. 169.
    Wing SS, Jain P (1995) Molecular cloning, expression and characterization of a ubiquitin conjugation enzyme (E2(17)kb) highly expressed in rat testis. Biochem J 305 (Part 1):125–132 Google Scholar
  170. 170.
    Wood A, Krogan NJ et al. (2003) Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell 11:267–274 PubMedCrossRefGoogle Scholar
  171. 171.
    Wood A, Schneider J et al. (2003) The PAF1 complex is essential for histone monoubiquitination by the Rad6/Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. J Biol Chem 278:34739–34742 PubMedCrossRefGoogle Scholar
  172. 172.
    Wood A, Schneider J et al. (2005) The Bur1/Bur2 complex is required for H2B monoubiquitination by Rad6/Bre and histone methylation by COMPASS. Mol Cell 20:589–599 PubMedCrossRefGoogle Scholar
  173. 173.
    Wu RS, Kohn KW et al. (1981) Metabolism of ubiquitinated histones. J Biol Chem 256:5916–5920 PubMedGoogle Scholar
  174. 174.
    Wysocka J, Swigut T et al. (2005) Wdr5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121:859–872 PubMedCrossRefGoogle Scholar
  175. 175.
    Wysocki R, Javaheri A et al. (2005) Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol 25:8430–8443 PubMedCrossRefGoogle Scholar
  176. 176.
    Xiao T, Hall H et al. (2003) Phosphorylation of RNA polymerase III CTD regulates H3 methylation in yeast. Genes Dev 17:654–663 PubMedCrossRefGoogle Scholar
  177. 177.
    Xiao T, Kao CF et al. (2005) Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol 25:637–651 PubMedCrossRefGoogle Scholar
  178. 178.
    Xie Y, Varshavsky A (1999) The E2-E3 interaction in the N-end rule pathway: the RING-H2 finger of E3 is required for the synthesis of multiubiquitin chain. EMBO J 18:6832–6844 PubMedCrossRefGoogle Scholar
  179. 179.
    Yamashita K, Shinohara M et al. (2004) Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci USA 101:11 380–11 385 CrossRefGoogle Scholar
  180. 180.
    Yao S, Neiman A et al. (2000) BUR1 and BUR2 encode a divergent cyclin-dependent kinase–cyclin complex important for transcription in vivo. Mol Cell Biol 20:7080–7087 PubMedCrossRefGoogle Scholar
  181. 181.
    Ye J, Ai X et al. (2005) Histone H4 lysine 91 acetylation, a core domain modification associated with chromatin assembly. Mol Cell 18:123–130 PubMedCrossRefGoogle Scholar
  182. 182.
    Zhang Y (2003) Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev 17:2733–2740 PubMedCrossRefGoogle Scholar
  183. 183.
    Zhang Y, Cao R et al. (2004) Mechanism of Polycomb group gene silencing. Cold Spring Harb Symp Quant Biol 69:309–317 PubMedCrossRefGoogle Scholar
  184. 184.
    Zhu B, Mandal SS et al. (2005) The human PAF complex coordinates transcription with events downstream of RNA synthesis. Genes Dev 19:1668–1673 PubMedCrossRefGoogle Scholar
  185. 185.
    Zhu B, Zheng Y et al. (2005) Monoubiquitination of human histone H2B: the factors involved and their roles in Hox gene regulation. Mol Cell 20:601–611 PubMedCrossRefGoogle Scholar

Authors and Affiliations

  • Mary Ann Osley
    • 1
  • Alastair B. Fleming
    • 1
  • Cheng-Fu Kao
    • 1
  1. 1.Molecular Genetics and MicrobiologyUniversity of New Mexico School of MedicineAlbuquerqueUSA

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