Genome wide analysis of nucleosome density histone acetylation and HDAC function in fission yeast

We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter‐localized repression. Hos2 has an unexpected role in promoting high expression of growth‐related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress‐ and meiosis‐induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.

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

[2]  D. Bentley,et al.  Altered nucleosome occupancy and histone H3K4 methylation in response to ‘transcriptional stress’ , 2005, The EMBO journal.

[3]  Saeed Tavazoie,et al.  Mapping Global Histone Acetylation Patterns to Gene Expression , 2004, Cell.

[4]  R. Lyne,et al.  The transcriptional program of meiosis and sporulation in fission yeast , 2002, Nature Genetics.

[5]  Eulàlia de Nadal,et al.  The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes , 2004, Nature.

[6]  S. Schreiber,et al.  Global nucleosome occupancy in yeast , 2004, Genome Biology.

[7]  R. Martienssen,et al.  Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries , 2005, Molecular and Cellular Biology.

[8]  Saeed Tavazoie,et al.  Genome-wide binding map of the histone deacetylase Rpd3 in yeast , 2002, Nature Genetics.

[9]  D. Reinberg,et al.  ING 1 Candidate Tumor Suppressor p 33 Complex in Growth Regulation by the Role of the Sin 3-Histone Deacetylase , 2001 .

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

[11]  J. Lieb,et al.  Evidence for nucleosome depletion at active regulatory regions genome-wide , 2004, Nature Genetics.

[12]  M. Grunstein,et al.  Centromere Silencing and Function in Fission Yeast Is Governed by the Amino Terminus of Histone H3 , 2003, Current Biology.

[13]  Michael Grunstein,et al.  Requirement of Hos2 Histone Deacetylase for Gene Activity in Yeast , 2002, Science.

[14]  D. Moazed,et al.  Sir2 Regulates Histone H3 Lysine 9 Methylation and Heterochromatin Assembly in Fission Yeast , 2003, Current Biology.

[15]  Ioannis Xenarios,et al.  Microarray Deacetylation Maps Determine Genome-Wide Functions for Yeast Histone Deacetylases , 2002, Cell.

[16]  S. Schreiber,et al.  A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p , 1996, Science.

[17]  Kevin Struhl,et al.  Evidence for Eviction and Rapid Deposition of Histones upon Transcriptional Elongation by RNA Polymerase II , 2004, Molecular and Cellular Biology.

[18]  J. Lieb,et al.  ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. , 2004, Genomics.

[19]  J Seth Strattan,et al.  Removal of promoter nucleosomes by disassembly rather than sliding in vivo. , 2004, Molecular cell.

[20]  Yoshio Masui,et al.  Understanding the cell cycle , 1998, Nature Medicine.

[21]  Martin Vingron,et al.  Genome-scale design of PCR primers and long oligomers for DNA microarrays. , 2003, Nucleic acids research.

[22]  Nicola J. Rinaldi,et al.  Global position and recruitment of HATs and HDACs in the yeast genome. , 2004, Molecular cell.

[23]  S. Schreiber,et al.  Genomewide studies of histone deacetylase function in yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Frye,et al.  Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. , 2000, Biochemical and biophysical research communications.

[25]  S. Forsburg,et al.  Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+ , 2005, Genetics.

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

[27]  J Wu,et al.  Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin. , 2001, Molecular cell.

[28]  S. Haas,et al.  A DNA microarray for fission yeast: minimal changes in global gene expression after temperature shift , 2004, Yeast.

[29]  A. Caudy,et al.  Functional Divergence between Histone Deacetylases in Fission Yeast by Distinct Cellular Localization and In Vivo Specificity , 2002, Molecular and Cellular Biology.

[30]  M. Grunstein,et al.  Genomewide histone acetylation microarrays. , 2003, Methods.

[31]  J Seth Strattan,et al.  Nucleosomes unfold completely at a transcriptionally active promoter. , 2003, Molecular cell.

[32]  A. Brazma,et al.  Global transcriptional responses of fission yeast to environmental stress. , 2003, Molecular biology of the cell.

[33]  B. Cairns,et al.  Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding region. , 2002, Molecular cell.

[34]  H. Reinke,et al.  Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. , 2003, Molecular cell.

[35]  R. Kobayashi,et al.  Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity , 2003, The EMBO journal.

[36]  S. Berger,et al.  Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. , 2000, Molecular cell.

[37]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[38]  M. Grunstein,et al.  TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. , 2001, Molecular cell.

[39]  M. Grunstein,et al.  HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. , 1996, Proceedings of the National Academy of Sciences of the United States of America.