title: Asf1/HIRA facilitate global histone deacetylation and associate with HP1 to promote nucleosome occupancy at heterochromatic loci.
abstract: Heterochromatin impacts various nuclear processes by providing a recruiting platform for diverse chromosomal proteins. In fission yeast, HP1 proteins Chp2 and Swi6, which bind to methylated histone H3 lysine 9, associate with SHREC (Snf2/HDAC repressor complex) and Clr6 histone deacetylases (HDACs) involved in heterochromatic silencing. However, heterochromatic silencing machinery is not fully defined. We describe a histone chaperone complex containing Asf1 and HIRA that spreads across silenced domains via its association with Swi6 to enforce transcriptional silencing. Asf1 functions in concert with a Clr6 HDAC complex to silence heterochromatic repeats, and it suppresses antisense transcription by promoting histone deacetylation. Furthermore, we demonstrate that Asf1 and SHREC facilitate nucleosome occupancy at heterochromatic regions but TFIIIC transcription factor binding sites within boundary elements are refractory to these factors. These analyses uncover a role for Asf1 in global histone deacetylation and suggest that HP1-associated histone chaperone promotes nucleosome occupancy to assemble repressive heterochromatin.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamane
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Bowen
authors.initials: B
authors.lastname: Cui
authors.forename: Martin
authors.initials: M
authors.lastname: Zofall
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Noma
authors.forename: Shiv I S
authors.initials: SI
authors.lastname: Grewal
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D016372:RNA, Antisense / Q000378:metabolism; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C524040:Cia1 protein, S pombe; C115302:Clr3 protein, S pombe; C115303:Clr6 protein, S pombe; D006570:Heterochromatin; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; D016372:RNA, Antisense; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D014157:Transcription Factors; C543473:hip1 protein, S pombe