A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation

Yu Yi Lin, Yan Qi, Jin Ying Lu, Xuewen Pan, Daniel S. Yuan, Yingming Zhao, Joel S. Bader, Jef D. Boeke

Research output: Contribution to journalArticle

Abstract

Histone acetylation and deacetylation are among the principal mechanisms by which chromatin is regulated during transcription, DNA silencing, and DNA repair. We analyzed patterns of genetic interactions uncovered during comprehensive genome-wide analyses in yeast to probe how histone acetyltransferase (HAT) and histone deacetylase (HDAC) protein complexes interact. The genetic interaction data unveil an underappreciated role of HDACs in maintaining cellular viability, and led us to show that deacetylation of the histone variant Htz1p at Lys 14 is mediated by Hda1p. Studies of the essential nucleosome acetyltransferase of H4 (NuA4) revealed acetylation-dependent protein stabilization of Yng2p, a potential nonhistone substrate of NuA4 and Rpd3C, and led to a new functional organization model for this critical complex. We also found that DNA double-stranded breaks (DSBs) result in local recruitment of the NuA4 complex, followed by an elaborate NuA4 remodeling process concomitant with Rpd3p recruitment and histone deacetylation. These new characterizations of the HDA and NuA4 complexes demonstrate how systematic analyses of genetic interactions may help illuminate the mechanisms of intricate cellular processes.

Original languageEnglish (US)
Pages (from-to)2062-2074
Number of pages13
JournalGenes and Development
Volume22
Issue number15
DOIs
StatePublished - Aug 1 2008

Keywords

  • Acetylation
  • DNA repair
  • Histone
  • NuA4
  • Systems biology

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Lin, Y. Y., Qi, Y., Lu, J. Y., Pan, X., Yuan, D. S., Zhao, Y., Bader, J. S., & Boeke, J. D. (2008). A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes and Development, 22(15), 2062-2074. https://doi.org/10.1101/gad.1679508