A dual role of H4K16 acetylation in the establishment of yeast silent chromatin

Mariano Oppikofer, Stephanie Kueng, Fabrizio Martino, Szabolcs Soeroes, Susan M. Hancock, Jason W. Chin, Wolfgang Fischle, Susan M. Gasser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Discrete regions of the eukaryotic genome assume heritable chromatin structure that is refractory to transcription. In budding yeast, silent chromatin is characterized by the binding of the Silent Information Regulatory (Sir) proteins to unmodified nucleosomes. Using an in vitro reconstitution assay, which allows us to load Sir proteins onto arrays of regularly spaced nucleosomes, we have examined the impact of specific histone modifications on Sir protein binding and linker DNA accessibility. Two typical marks for active chromatin, H3K79me and H4K16ac decrease the affinity of Sir3 for chromatin, yet only H4K16ac affects chromatin structure, as measured by nuclease accessibility. Surprisingly, we found that the Sir2-4 subcomplex, unlike Sir3, has higher affinity for chromatin carrying H4K16 ac. NAD-dependent deacetylation of H4K16ac promotes binding of the SIR holocomplex but not of the Sir2-4 heterodimer. This function of H4K16ac cannot be substituted by H3K56ac. We conclude that acetylated H4K16 has a dual role in silencing: it recruits Sir2-4 and repels Sir3. Moreover, the deacetylation of H4K16ac by Sir2 actively promotes the high-affinity binding of the SIR holocomplex.

Original languageEnglish (US)
Pages (from-to)2610-2621
Number of pages12
JournalEMBO Journal
Volume30
Issue number13
DOIs
StatePublished - Jul 6 2011

Keywords

  • H4K16
  • SIR complex
  • histone deacetylation
  • methylation
  • silent chromatin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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