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A dual role of H4K16 acetylation in the establishment of yeast silent chromatin
Author(s) -
Oppikofer Mariano,
Kueng Stephanie,
Martino Fabrizio,
Soeroes Szabolcs,
Hancock Susan M,
Chin Jason W,
Fischle Wolfgang,
Gasser Susan M
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.170
Subject(s) - biology , acetylation , chromatin , yeast , histone , epigenetics , microbiology and biotechnology , genetics , epigenesis , dna , dna methylation , gene , gene expression
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, H3K79 me and H4K16 ac decrease the affinity of Sir3 for chromatin, yet only H4K16 ac 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 H4K16 ac promotes binding of the SIR holocomplex but not of the Sir2‐4 heterodimer. This function of H4K16 ac cannot be substituted by H3K56 ac . We conclude that acetylated H4K16 has a dual role in silencing: it recruits Sir2‐4 and repels Sir3. Moreover, the deacetylation of H4K16 ac by Sir2 actively promotes the high‐affinity binding of the SIR holocomplex.