The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast

Takatomi Yamada, Wolfgang Fischle, Tomoyasu Sugiyama, C. David Allis, Shiv I.S. Grewal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

Posttranslational modifications of histones play an essential role in heterochromatin assembly. Whereas the role of Clr4/Suv39h-mediated methylation of histone H3 at lysine 9 (H3K9) in heterochromatin assembly is well studied, the exact function of histone deacetylases (HDACs) in this process is unclear. We show that Clr3, a fission yeast homolog of mammalian class II HDACs, acts in a distinct pathway parallel to RNAi-directed heterochromatin nucleation to recruit Clr4 and mediate H3K9 methylation at the silent mating-type region and centromeres. At the mat locus, Clr3 is recruited at a specific site through a mechanism involving ATF/CREB family proteins. Once recruited, Clr3 spreads across the 20 kb silenced domain that requires its own HDAC activity and heterochromatin proteins including Swi6/HP1. We also demonstrate that Clr3 contributes to heterochromatin maintenance by stabilizing H3K9 trimethylation and by preventing histone modifications associated with active transcription, and that it limits RNA polymerase II accessibility to naturally silenced repeats at heterochromatin domains.

Original languageEnglish (US)
Pages (from-to)173-185
Number of pages13
JournalMolecular cell
Volume20
Issue number2
DOIs
StatePublished - Oct 28 2005
Externally publishedYes

Bibliographical note

Funding Information:
We thank J. Petersen, I. Hagan, and M. Yanagida for providing strains; J. Nakayama, S. Jia, and K. Noma for helpful contributions; H. Cam for assistance in manuscript preparation; and members of the Grewal laboratory for stimulating discussions. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and NIH grants (to C.D.A.). W.F. is supported by a Damon Runyon postdoctoral fellowship, and T.S. is a JSPS Fellow in Biomedical and Behavioral Research at the U.S. National Institutes of Health.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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