title: Histone H2B ubiquitylation and H3 lysine 4 methylation prevent ectopic silencing of euchromatic loci important for the cellular response to heat.
abstract: 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 we 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 the cellular response to heat-whose expression is attenuated by loss of H2B ubiquitylation but restored by disruption of Sir 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.
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Leung
authors.forename: Ivelisse
authors.initials: I
authors.lastname: Cajigas
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.forename: Elena
authors.initials: E
authors.lastname: Ezhkova
authors.forename: Jason H
authors.initials: JH
authors.lastname: Brickner
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Geng
authors.forename: William P
authors.initials: WP
authors.lastname: Tansey
mesh_terms: D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D022041:Euchromatin / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D056426:Genetic Loci; D016681:Genome, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D017422:Sequence Analysis, DNA; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D054875:Ubiquitination
chemical_list: D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D008239:Lysine