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Genome-wide patterns of histone modifications in yeast

Nature Reviews Molecular Cell Biology volume 7, pages 657–666 (2006)Cite this article

Key Points

  • The availability of antibodies that are directed against specific histone-modification sites has allowed the mapping of these sites at the whole-genome level using microarrays. Recent data in Saccharomyces cerevisiae are analysed to ask whether unique histone-modification patterns have specific functions.

  • The preferences of enzymes for particular histone sites and chromosomal locations are described. Different enzymes can affect the same genomic regions to generate unique patterns of modifications.

  • In particular, there are differences between the histone-modification patterns of heterochromatin, subtelomeric heterochromatin-adjacent regions, centromeric chromatin, promoters and coding regions. The roles of histone-modification patterns at these domains are discussed.

  • The fully deacetylated, demethylated state is necessary for repression of gene activity in heterochromatin. Domains that are partially deacetylated might be activated more easily.

  • Both acetylation and deacetylation are important for gene activity. Certain sites, including H4K16, are hypoacetylated at active genes, and histone deacetylases that deacetylate H4K16 (for example, Hos2) have also been described as activators of transcription.

  • Hypoacetylation and methylation of certain lysine residues have been shown to affect the binding of chromosomal proteins to target genes. These studies also provide a link between the methylation of a lysine residue (H3K36) and the recruitment of the histone deacetylase Rpd3 to a gene.

  • Finally, the availability of similar studies in Schizosaccharomyces pombe, which is widely divergent in evolution from S. cerevisiae, suggests that the findings above might be extrapolated to other eukaryotes.

Abstract

Post-translational histone modifications and histone variants generate complexity in chromatin to enable the many functions of the chromosome. Recent studies have mapped histone modifications across the Saccharomyces cerevisiae genome. These experiments describe how combinations of modified and unmodified states relate to each other and particularly to chromosomal landmarks that include heterochromatin, subtelomeric chromatin, centromeres, origins of replication, promoters and coding regions. Such patterns might be important for the regulation of heterochromatin-mediated silencing, chromosome segregation, DNA replication and gene expression.

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Figure 1: Known sites of histone modifications and some of the modifying enzymes in Saccharomyces cerevisiae.
Figure 2: Chromosomal domains with different combinations of histone modifications.
Figure 3: Gradients of histone methylation and acetylation in active genes.
Figure 4: Patterns of histone acetylation in Saccharomyces cerevisiae.

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References

  1. Grunstein, M. Histone function in transcription. Annu. Rev. Cell Biol. 6, 643–678 (1990).

    CAS  PubMed  Google Scholar 

  2. Cheung, W. L., Briggs, S. D. & Allis, C. D. Acetylation and chromosomal functions. Curr. Opin. Cell Biol. 12, 326–333 (2000).

    CAS  PubMed  Google Scholar 

  3. Martin, C. & Zhang, Y. The diverse functions of histone lysine methylation. Nature Rev. Mol. Cell Biol. 6, 838–849 (2005).

    CAS  Google Scholar 

  4. Johnson, L. M., Kayne, P. S., Kahn, E. S. & Grunstein, M. Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 87, 6286–6290 (1990).

    CAS  PubMed  Google Scholar 

  5. Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599 (2000).

    CAS  PubMed  Google Scholar 

  6. Braunstein, M., Rose, A. B., Holmes, S. G., Allis, C. D. & Broach, J. R. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 7, 592–604 (1993).

    CAS  PubMed  Google Scholar 

  7. Vogelauer, M., Rubbi, L., Lucas, I., Brewer, B. J. & Grunstein, M. Histone acetylation regulates the time of replication origin firing. Mol. Cell 10, 1223–1233 (2002).

    CAS  PubMed  Google Scholar 

  8. Ahn, S. H. et al. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120, 25–36 (2005).

    CAS  PubMed  Google Scholar 

  9. van Attikum, H. & Gasser, S. M. The histone code at DNA breaks: a guide to repair? Nature Rev. Mol. Cell Biol. 6, 757–765 (2005).

    CAS  Google Scholar 

  10. Kurdistani, S. K., Tavazoie, S. & Grunstein, M. Mapping global histone acetylation patterns to gene expression. Cell 117, 721–733 (2004). Genome-wide comparison of many histone acetylation sites in S. cerevisiae , which shows that sites are acetylated differentially, generating patterns that correlate with gene activity.

    CAS  PubMed  Google Scholar 

  11. Smith, C. M. et al. Mass spectrometric quantification of acetylation at specific lysines within the amino-terminal tail of histone H4. Anal. Biochem. 316, 23–33 (2003).

    CAS  PubMed  Google Scholar 

  12. Boyne, M. T. 2nd, Pesavento, J. J., Mizzen, C. A. & Kelleher, N. L. Precise characterization of human histones in the H2A gene family by top down mass spectrometry. J. Proteome Res. 5, 248–253 (2006).

    CAS  PubMed  Google Scholar 

  13. Thomas, C. E., Kelleher, N. L. & Mizzen, C. A. Mass spectrometric characterization of human histone H3: a bird's eye view. J. Proteome Res. 5, 240–247 (2006).

    CAS  PubMed  Google Scholar 

  14. Clarke, D. J., O'Neill, L. P. & Turner, B. M. Selective use of H4 acetylation sites in the yeast Saccharomyces cerevisiae. Biochem. J. 294, 557–561 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Turner, B. M., O'Neill, L. P. & Allan, I. M. Histone H4 acetylation in human cells. Frequency of acetylation at different sites defined by immunolabeling with site-specific antibodies. FEBS Lett. 253, 141–145 (1989).

    CAS  PubMed  Google Scholar 

  16. Suka, N., Suka, Y., Carmen, A. A., Wu, J. & Grunstein, M. Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin. Mol. Cell 8, 473–479 (2001).

    CAS  PubMed  Google Scholar 

  17. Sarma, K., Nishioka, K. & Reinberg, D. Tips in analyzing antibodies directed against specific histone tail modifications. Methods Enzymol. 376, 255–269 (2004).

    CAS  PubMed  Google Scholar 

  18. Kurdistani, S. K. & Grunstein, M. In vivo protein–protein and protein–DNA crosslinking for genomewide binding microarray. Methods 31, 90–95 (2003).

    CAS  PubMed  Google Scholar 

  19. Robyr, D. & Grunstein, M. Genomewide histone acetylation microarrays. Methods 31, 83–89 (2003).

    CAS  PubMed  Google Scholar 

  20. Rao, B., Shibata, Y., Strahl, B. D. & Lieb, J. D. Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide. Mol. Cell. Biol. 25, 9447–9459 (2005). Genome-wide study of H3K36 methylation, which shows that this modification is restricted to the coding regions of active genes.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu, C. L. et al. Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol. 3, e328 (2005). Describes the mapping of histone modifications at single-nucleosome resolution on S. cerevisiae chromosome III, and shows that the modification pattern of nucleosomes surrounding the transcription start site differs from that of coding-region nucleosomes.

    PubMed  PubMed Central  Google Scholar 

  22. Pokholok, D. K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005). High-resolution, genome-wide analysis of S. cerevisiae chromosomes, which shows that acetylation at sites in H3 correlates with transcription.

    CAS  PubMed  Google Scholar 

  23. Xu, F., Zhang, K. & Grunstein, M. Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121, 375–385 (2005).

    CAS  PubMed  Google Scholar 

  24. Millar, C. B., Xu, F., Zhang, K. & Grunstein, M. Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast. Genes Dev. 20, 711–722 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Wiren, M. et al. Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast. EMBO J. 24, 2906–2918 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Cam, H. P. et al. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nature Genet. 37, 809–819 (2005).

    CAS  PubMed  Google Scholar 

  27. Schubeler, D. et al. The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev. 18, 1263–1271 (2004).

    PubMed  PubMed Central  Google Scholar 

  28. Mito, Y., Henikoff, J. G. & Henikoff, S. Genome-scale profiling of histone H3.3 replacement patterns. Nature Genet. 37, 1090–1097 (2005).

    CAS  PubMed  Google Scholar 

  29. Bernstein, B. E. et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120, 169–181 (2005).

    CAS  PubMed  Google Scholar 

  30. Nishida, H. et al. Histone H3 acetylated at lysine 9 in promoter is associated with low nucleosome density in the vicinity of transcription start site in human cell. Chromosome Res. 14, 203–211 (2006).

    CAS  PubMed  Google Scholar 

  31. Tse, C., Sera, T., Wolffe, A. P. & Hansen, J. C. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Mol. Cell. Biol. 18, 4629–4638 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Zheng, C. & Hayes, J. J. Intra- and inter-nucleosomal protein–DNA interactions of the core histone tail domains in a model system. J. Biol. Chem. 278, 24217–24224 (2003).

    CAS  PubMed  Google Scholar 

  33. Dorigo, B., Schalch, T., Bystricky, K. & Richmond, T. J. Chromatin fiber folding: requirement for the histone H4 N-terminal tail. J. Mol. Biol. 327, 85–96 (2003).

    CAS  PubMed  Google Scholar 

  34. Shogren-Knaak, M. et al. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311, 844–847 (2006). Shows that acetylation of a single site (K16) in H4 regulates higher orders of folding of nucleosome arrays in vitro.

    CAS  PubMed  Google Scholar 

  35. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001). Identifies the chromodomain as a methyl-lysine-binding module.

    CAS  PubMed  Google Scholar 

  36. Huyen, Y. et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432, 406–411 (2004).

    CAS  PubMed  Google Scholar 

  37. Wysocka, J. et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121, 859–872 (2005).

    CAS  PubMed  Google Scholar 

  38. Kim, J. et al. Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep. 7, 397–403 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491–496 (1999). Identifies the bromodomain as an acetyl-lysine-recognition domain.

    CAS  PubMed  Google Scholar 

  40. Jacobson, R. H., Ladurner, A. G., King, D. S. & Tjian, R. Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425 (2000).

    CAS  PubMed  Google Scholar 

  41. Zeng, L. & Zhou, M. M. Bromodomain: an acetyl-lysine binding domain. FEBS Lett. 513, 124–128 (2002).

    CAS  PubMed  Google Scholar 

  42. Carmen, A. A., Milne, L. & Grunstein, M. Acetylation of the yeast histone H4 N terminus regulates its binding to heterochromatin protein SIR3. J. Biol. Chem. 277, 4778–4781 (2002).

    CAS  PubMed  Google Scholar 

  43. Liou, G. G., Tanny, J. C., Kruger, R. G., Walz, T. & Moazed, D. Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation. Cell 121, 515–527 (2005). Shows that acetylation of H4K16 disrupts interaction between full-length Sir3 and a peptide that corresponds to the N terminus of H4.

    CAS  PubMed  Google Scholar 

  44. Rayasam, G. V. et al. NSD1 is essential for early post-implantation development and has a catalytically active SET domain. EMBO J. 22, 3153–163 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang, A., Kurdistani, S. K. & Grunstein, M. Requirement of Hos2 histone deacetylase for gene activity in yeast. Science 298, 1412–1414 (2002).

    CAS  PubMed  Google Scholar 

  46. Imai, S. et al. Sir2: an NAD-dependent histone deacetylase that connects chromatin silencing, metabolism, and aging. Cold Spring Harb. Symp. Quant. Biol. 65, 297–302 (2000).

    CAS  PubMed  Google Scholar 

  47. Landry, J. et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc. Natl Acad. Sci. USA 97, 5807–5811 (2000).

    CAS  PubMed  Google Scholar 

  48. Sutton, A. et al. Sas4 and Sas5 are required for the histone acetyltransferase activity of Sas2 in the SAS complex. J. Biol. Chem. 278, 16887–16892 (2003).

    CAS  PubMed  Google Scholar 

  49. Kimura, A., Umehara, T. & Horikoshi, M. Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Nature Genet. 32, 370–377 (2002).

    PubMed  Google Scholar 

  50. Suka, N., Luo, K. & Grunstein, M. Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nature Genet. 32, 378–383 (2002).

    CAS  PubMed  Google Scholar 

  51. Reid, J. L., Iyer, V. R., Brown, P. O. & Struhl, K. Coordinate regulation of yeast ribosomal protein genes is associated with targeted recruitment of Esa1 histone acetylase. Mol. Cell 6, 1297–1307 (2000).

    CAS  PubMed  Google Scholar 

  52. Kadosh, D. & Struhl, K. Targeted recruitment of the Sin3–Rpd3 histone deacetylase complex generates a highly localized domain of repressed chromatin in vivo. Mol. Cell. Biol. 18, 5121–5127 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Kurdistani, S. K., Robyr, D., Tavazoie, S. & Grunstein, M. Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nature Genet. 31, 248–254 (2002).

    CAS  PubMed  Google Scholar 

  54. Robert, F. et al. Global position and recruitment of HATs and HDACs in the yeast genome. Mol. Cell 16, 199–209 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Vogelauer, M., Wu, J., Suka, N. & Grunstein, M. Global histone acetylation and deacetylation in yeast. Nature 408, 495–498 (2000).

    CAS  PubMed  Google Scholar 

  56. Boudreault, A. A. et al. Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin. Genes Dev. 17, 1415–1428 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Waterborg, J. H. Steady-state levels of histone acetylation in Saccharomyces cerevisiae. J. Biol. Chem. 275, 13007–13011 (2000).

    CAS  PubMed  Google Scholar 

  58. Grunstein, M. Yeast heterochromatin: regulation of its assembly and inheritance by histones. Cell 93, 325–328 (1998).

    CAS  PubMed  Google Scholar 

  59. Ng, H. H., Robert, F., Young, R. A. & Struhl, K. 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 (2003).

    CAS  PubMed  Google Scholar 

  60. Xiao, T. et al. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 17, 654–663 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Keogh, M. C. et al. Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123, 593–605 (2005).

    CAS  PubMed  Google Scholar 

  62. Joshi, A. A. & Struhl, K. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol. Cell 20, 971–978 (2005).

    CAS  PubMed  Google Scholar 

  63. Carrozza, M. J. et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123, 581–592 (2005).

    CAS  PubMed  Google Scholar 

  64. Shahbazian, M. D., Zhang, K. & Grunstein, M. Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Mol. Cell 19, 271–277 (2005).

    CAS  PubMed  Google Scholar 

  65. Cubizolles, F., Martino, F., Perrod, S. & Gasser, S. M. A homotrimer–heterotrimer switch in Sir2 structure differentiates rDNA and telomeric silencing. Mol. Cell 21, 825–836 (2006).

    CAS  PubMed  Google Scholar 

  66. Robyr, D. et al. Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109, 437–446 (2002). First genome-wide analysis of histone modifications, which identifies unique chromosomal domains that are affected by specific histone deacetylases in S. cerevisiae.

    CAS  PubMed  Google Scholar 

  67. Katan-Khaykovich, Y. & Struhl, K. Heterochromatin formation involves changes in histone modifications over multiple cell generations. EMBO J. 24, 2138–2149 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Hecht, A., Laroche, T., Strahl-Bolsinger, S., Gasser, S. M. & Grunstein, M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell 80, 583–592 (1995).

    CAS  PubMed  Google Scholar 

  69. Donze, D., Adams, C. R., Rine, J. & Kamakaka, R. T. The boundaries of the silenced HMR domain in Saccharomyces cerevisiae. Genes Dev. 13, 698–708 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Thompson, J. S., Ling, X. & Grunstein, M. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Nature 369, 245–247 (1994).

    CAS  PubMed  Google Scholar 

  71. Sullivan, B. A. & Karpen, G. H. Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nature Struct. Mol. Biol. 11, 1076–1083 (2004).

    CAS  Google Scholar 

  72. Blower, M. D., Sullivan, B. A. & Karpen, G. H. Conserved organization of centromeric chromatin in flies and humans. Dev. Cell 2, 319–330 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Meluh, P. B., Yang, P., Glowczewski, L., Koshland, D. & Smith, M. M. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94, 607–613 (1998).

    CAS  Google Scholar 

  74. Riedel, C. G. et al. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441, 53–61 (2006).

    CAS  PubMed  Google Scholar 

  75. Masumoto, H., Hawke, D., Kobayashi, R. & Verreault, A. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature 436, 294–298 (2005).

    CAS  PubMed  Google Scholar 

  76. Wu, J., Suka, N., Carlson, M. & Grunstein, M. TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. Mol. Cell 7, 117–126 (2001).

    CAS  PubMed  Google Scholar 

  77. Meneghini, M. D., Wu, M. & Madhani, H. D. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112, 725–36 (2003). Identification of groups of subtelomeric genes, the expression of which is regulated by the histone variant H2A.Z.

    CAS  PubMed  Google Scholar 

  78. Raisner, R. M. et al. Histone variant H2A. Z marks the 5′ ends of both active and inactive genes in euchromatin. Cell 123, 233–248 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Zhang, H., Roberts, D. N. & Cairns, B. R. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123, 219–231 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Guillemette, B. et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol. 3, e384 (2005).

    PubMed  PubMed Central  Google Scholar 

  81. Li, B. et al. Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling. Proc. Natl Acad. Sci. USA 102, 18385–18390 (2005).

    CAS  PubMed  Google Scholar 

  82. Aparicio, J. G., Viggiani, C. J., Gibson, D. G. & Aparicio, O. M. The Rpd3–Sin3 histone deacetylase regulates replication timing and enables intra-S origin control in Saccharomyces cerevisiae. Mol. Cell. Biol. 24, 4769–4780 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Boeger, H., Griesenbeck, J., Strattan, J. S. & Kornberg, R. D. Removal of promoter nucleosomes by disassembly rather than sliding in vivo. Mol. Cell 14, 667–673 (2004).

    CAS  PubMed  Google Scholar 

  84. Reinke, H. & Horz, W. Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol. Cell 11, 1599–1607 (2003).

    CAS  PubMed  Google Scholar 

  85. Adkins, M. W., Howar, S. R. & Tyler, J. K. Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes. Mol. Cell 14, 657–666 (2004).

    CAS  PubMed  Google Scholar 

  86. Korber, P. et al. The histone chaperone Asf1 increases the rate of histone eviction at the yeast PHO5 and PHO8 promoters. J. Biol. Chem. 281, 5539–5545 (2006).

    CAS  PubMed  Google Scholar 

  87. Lee, C. K., Shibata, Y., Rao, B., Strahl, B. D. & Lieb, J. D. Evidence for nucleosome depletion at active regulatory regions genome-wide. Nature Genet. 36, 900–905 (2004).

    CAS  PubMed  Google Scholar 

  88. Bernstein, B. E., Liu, C. L., Humphrey, E. L., Perlstein, E. O. & Schreiber, S. L. Global nucleosome occupancy in yeast. Genome Biol. 5, R62 (2004).

    PubMed  PubMed Central  Google Scholar 

  89. Struhl, K., Kadosh, D., Keaveney, M., Kuras, L. & Moqtaderi, Z. Activation and repression mechanisms in yeast. Cold Spring Harb. Symp. Quant. Biol. 63, 413–421 (1998).

    CAS  PubMed  Google Scholar 

  90. Krebs, J. E., Kuo, M. H., Allis, C. D. & Peterson, C. L. Cell cycle-regulated histone acetylation required for expression of the yeast HO gene. Genes Dev. 13, 1412–1421 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Kuo, M. H., vom Baur, E., Struhl, K. & Allis, C. D. Gcn4 activator targets Gcn5 histone acetyltransferase to specific promoters independently of transcription. Mol. Cell 6, 1309–1320 (2000).

    CAS  PubMed  Google Scholar 

  92. Zhao, J., Herrera-Diaz, J. & Gross, D. S. Domain-wide displacement of histones by activated heat shock factor occurs independently of Swi/Snf and is not correlated with RNA polymerase II density. Mol. Cell. Biol. 25, 8985–8999 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Guo, X., Tatsuoka, K. & Liu, R. Histone acetylation and transcriptional regulation in the genome of Saccharomyces cerevisiae. Bioinformatics 22, 392–399 (2006).

    CAS  PubMed  Google Scholar 

  94. Matangkasombut, O., Buratowski, R. M., Swilling, N. W. & Buratowski, S. Bromodomain factor 1 corresponds to a missing piece of yeast TFIID. Genes Dev. 14, 951–962 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Eisen, A. et al. The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation. J. Biol. Chem. 276, 3484–3491 (2001).

    CAS  PubMed  Google Scholar 

  96. Hassan, A. H. et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111, 369–379 (2002).

    CAS  PubMed  Google Scholar 

  97. Kasten, M. et al. Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14. EMBO J. 23, 1348–1359 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Ladurner, A. G., Inouye, C., Jain, R. & Tjian, R. Bromodomains mediate an acetyl-histone encoded antisilencing function at heterochromatin boundaries. Mol. Cell 11, 365–376 (2003).

    CAS  PubMed  Google Scholar 

  99. Matangkasombut, O. & Buratowski, S. Different sensitivities of bromodomain factors 1 and 2 to histone H4 acetylation. Mol. Cell 11, 353–363 (2003).

    CAS  PubMed  Google Scholar 

  100. Shankaranarayana, G. D., Motamedi, M. R., Moazed, D. & Grewal, S. I. Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast. Curr. Biol. 13, 1240–1246 (2003).

    CAS  PubMed  Google Scholar 

  101. Wirbelauer, C., Bell, O. & Schubeler, D. Variant histone H3.3 is deposited at sites of nucleosomal displacement throughout transcribed genes while active histone modifications show a promoter-proximal bias. Genes Dev. 19, 1761–1766 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Sinha, I., Wiren, M. & Ekwall, K. Genome-wide patterns of histone modifications in fission yeast. Chromosome Res. 14, 95–105 (2006).

    CAS  PubMed  Google Scholar 

  103. Ahmad, K. & Henikoff, S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol. Cell 9, 1191–1200 (2002).

    CAS  PubMed  Google Scholar 

  104. De Nadal, E. et al. The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427, 370–374 (2004).

    CAS  PubMed  Google Scholar 

  105. Grant, P. A., et al. Expanded lysine acetylation specificity of Gcn5 in native complexes. J. Biol Chem. 274, 5895–5900 (1999).

    CAS  PubMed  Google Scholar 

  106. Maas, N. L., Miller, K. M., DeFazio, L. G. & Toczyski, D. P. Cell cycle and checkpoint regulation of histone H3K56 acetylation by Hst3 and Hst4. Mol. Cell 23, 109–119 (2006).

    CAS  PubMed  Google Scholar 

  107. Celic, I. et al. The sirtuins Hst3 and Hst4p preserve genome integrity by controlling histone H3 lysine 56 deacetylation. Curr. Biol. 16, 1280–1289 (2006).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank members of the Grunstein laboratory and S. Kurdistani for comments on the manuscript. This work was supported by a Wellcome Trust International Research Fellowship to C.B.M. and Public Service grants Health Service grants from the National Institutes of Health to M.G.

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  1. Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, 90095, California, USA

    Catherine B. Millar & Michael Grunstein

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  1. Catherine B. Millar
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DATABASES

Saccharomyces Genome Database

Abf1

Asf1

Bdf1

Bdf2

Cse4

Dot1

Eaf3

Esa1

Hda1

Hos1

Hos2

Hos3

Hst1

Hst3

Hst4

Htz1

INO1

PHO5

Rpd3

Sas2

Set1

Set2

Sir2

Sir3

Sir4

Spt10

Sum1

Ume6

FURTHER INFORMATION

Michael Grunstein's homepage

Glossary

Heterochromatin

A form of chromatin that is condensed throughout the cell cycle and is transcriptionally less active than euchromatin.

Chromatin immunoprecipitation

(ChIP). A method for determining whether a protein binds to a specific region of the genome in vivo. Live cells are treated with a crosslinking agent to form nonspecific crosslinks between the DNA and associated proteins. After shearing the chromatin into small fragments, the protein of interest is immunoprecipitated. Any protein-associated DNA is then analysed by quantitative PCR, cloning, sequencing or hybridization to microarrays (ChIP-on-chip).

Chromodomain

A conserved protein structure that is common to some chromosomal proteins. This domain interacts with chromatin by binding to methylated lysine residues in histone proteins.

WD40 domain

A 40-amino-acid protein motif that contains a WD dipeptide at its C terminus. This domain is found in many functionally diverse proteins and mediates protein–protein interactions.

Tudor domain

A domain that is related to the chromodomain and that binds methylated arginine and lysine residues.

MBT domain

A domain that is present in several transcriptional repressors that bind to methylated lysine residues.

Bromodomain

A domain that is present in many chromatin-associated proteins and that binds to acetylated lysine residues.

MYST-class HAT

A family of histone acetyltransferases that are related at the sequence level and that are named after the founding members, MOZ, Ybf2/Sas3, Sas2 and Tip60.

SIR silencing complex

A complex comprising Sir2, Sir3 and Sir4 that binds to heterochromatic regions through Sir3 and Sir4, and deacetylates histones as a result of the HDAC activity of Sir2.

Euchromatin

The non-heterochromatic portion of the genome that includes both repressed and active genes.

Hda1-affected subtelomeric (HAST) domain

Groups of contiguous genes that are deacetylated by the HDAC Hda1, and are located in the subtelomeric euchromatin.

Htz1-activated domain

(HZAD). Adjacent sub-telomeric genes, the expression of which is downregulated in the absence of the H2A variant Htz1.

Histone variant

A histone protein that differs in primary sequence from a major core histone but can substitute for it in nucleosomes.

Kinetochore

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

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Millar, C., Grunstein, M. Genome-wide patterns of histone modifications in yeast. Nat Rev Mol Cell Biol 7, 657–666 (2006). https://doi.org/10.1038/nrm1986

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