Histone H2B ubiquitylation and H3 lysine 4 methylation prevent ectopic silencing of euchromatic loci important for the cellular response to heat

  • Amy Leung (Contributor)
  • Ivelisse Cajigas (Contributor)
  • Peilin Jia (Contributor)
  • Elena Ezhkova (Contributor)
  • Zhongming Zhao (Contributor)
  • Fuqiang Geng (Contributor)



In Saccharomyces cerevisiae, ubiquitylation of histone H2B signals methylation of histone H3 at lysine residues 4 (K4) and 79. These modifications occur at active genes but are believed to stabilize silent chromatin by limiting movement of silencing proteins away from heterochromatin domains. In the course of studying atypical phenotypes associated with loss of H2B ubiquitylation/H3K4 methylation, we discovered that these modifications are also required for cell wall integrity at high temperatures. We identified the silencing protein Sir4 as a dosage-suppressor of loss of H2B ubiquitylation, and showed that elevated Sir4 expression suppresses cell wall integrity defects by inhibiting the function of the Sir silencing complex. Using comparative transcriptome analysis, we identified a set of euchromatic genes - enriched in those required for cellular response to heat - whose expression is attenuated by loss of H2B ubiquitylation, but restored by disruption of Sir protein function. Finally, using DNA adenine methyltransferase identification, we found that Sir3 and Sir4 associate with genes that are silenced in the absence of H3K4 methylation. Our data reveal that H2B ubiquitylation/H3K4 methylation play an important role in limiting ectopic association of silencing proteins with euchromatic genes important for cell wall integrity and the response to heat. The transcriptome of four strains, wildtype, htbK123R, sir4delta,and htbK123R sir4delta, were sequenced using Illumina sequencing technology
Date made available2011

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