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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 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.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE27934 | GEO | 2011/12/02

SECONDARY ACCESSION(S): PRJNA137859

REPOSITORIES: GEO

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

Project description: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

2011-12-02 | E-GEOD-27934 | biostudies-arrayexpress

Sir4 H-BRCT domain interacts with multiple phospho-proteins to regulate heterochromatic repression

Project description:In Saccharomyces cerevisiae, the Silent Information Regulator (SIR) proteins Sir2/3/4 form a complex suppressing transcription of genes at subtelomeric regions and the homothallic mating type (HM) loci. Here we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in Sir4 which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H-BRCT and the closely related Dbf4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H-BRCT, including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with Sir4 H-BRCT and Dbf4 H-BRCT. Ablation of the Sir4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the Sir4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.

2019-09-13 | PXD014119 | Pride

Genome-Wide Microarray Analysis of Histone H2B Ubiquitylation mutant strains of Tetrahymena thermophila

Project description:Microarray analyses were performed to compare the gene expression profiles of wild-type and several mutant strains of the ciliated protozoan Tetrahymena thermophila. Elimination of H3K4 methylation (hht2-K4Q) and knockout of either of the ubiquitylation enzymes (delta-UBC2 and delta-BRE1) affects a broader spectrum of genes than elimination of H2B ubiquitylation (htb1-K115R).

2009-10-27 | GSE18743 | GEO

Genome-Wide Microarray Analysis of Histone H2B Ubiquitylation mutant strains of Tetrahymena thermophila

2010-06-20 | E-GEOD-18743 | biostudies-arrayexpress

Context dependent function of transcriptional regulator Rap1 in gene silencing and activation [ChIP-seq III]

Project description:As part of a study on the mechanism of Sir-based silencing at HML in S.cerevisiae, and the contribution of Rap1 to transcription of the locus, we performed ChIP-seq of multiple components of RNA Pol II machinery in different genetic backgrounds including: sir4∆, SIR+, and with or without a mutation that abbrogated Rap1 binding at the alpha promoter.

2023-05-09 | GSE227760 | GEO

Histone H2B ubiquitylation represses gametogenesis by opposing RSC-Dependent chromatin remodeling at the ste11 master regulator locus

Project description:Chromatin modifications play a pivotal role in cell fate decision. In fission yeast, the ste11 gene encodes the master regulator initiating the switch from vegetative growth to gametogenesis when cells starve. The methylation of H3K4 by Set1-COMPASS and consequent promoter nucleosome deacetylation was shown to repress ste11 induction and cell differentiation but the regulatory steps remain poorly understood. A genetic screen highlighted H2B ubiquitylation and the RSC remodeling complex as activators of ste11 expression. Mechanistic analyses revealed more complex, opposite roles of H2B-ub1 at the promoter where it represses expression, and over the transcribed region where it sustains transcription of ste11. By promoting H3K4 methylation at the promoter, H2B-ub1 initiates the deacetylation process, which decreases chromatin remodeling by RSC. Upon induction, this process is reversed and efficient NDR formation leads to high expression. Therefore, H2B-ub1 represses gametogenesis by opposing the recruitment of RSC at the promoter of the master regulator ste11 gene. Samples from mononucleosomal DNA from S. pombe strains h-972 and h-972 rsc1::kanR were sequenced (Illumina NextSeq 500 platform) using the pair-end read protocol

2016-07-22 | E-GEOD-80524 | biostudies-arrayexpress

Histone H2B ubiquitylation represses gametogenesis by opposing RSC-Dependent chromatin remodeling at the ste11 master regulator locus

2016-07-22 | GSE80524 | GEO

Dynamic loss of H2B ubiquitylation without corresponding changes in H3K4 tri-methylation during myogenic differentiation

Project description:Ubiquitylation of H2B on lysine 120 (H2Bub) is associated with active transcriptional elongation. H2Bub has been implicated in histone cross-talk and is generally regarded to be a prerequisite for H3K4 and H3K79 tri-methylation in both yeast and mammalian cells. We performed a genome-wide analysis of epigenetic marks during muscle differentiation, and, strikingly, we observed a near-complete loss of H2Bub in the differentiated state. We examined the basis for global loss of this mark and found that the H2B ubiquitin E3 ligase, RNF20, was depleted from chromatin in differentiated myotubes, indicating that recruitment of this protein to genes substantially decreases upon differentiation. Remarkably, during the course of myogenic differentiation, we observed retention and acquisition of H3K4 tri-methylation on a large number of genes in the absence of detectable H2Bub. The Set1 H3K4 trimethylase complex was efficiently recruited to a subset of genes in myotubes in the absence of detectable H2Bub, accounting in part for H3K4 tri-methylation in myotubes. Our studies suggest that H3K4me3 deposition in the absence of detectable H2Bub in myotubes is mediated via Set1 and, perhaps, MLL complexes, whose recruitment does not require H2Bub. Thus, muscle cells represent a novel setting in which to explore mechanisms that regulate histone cross-talk. Mapping of H2Bub in growing myoblasts (MB) and fully differentiated myotubes (MT).

2012-03-06 | E-GEOD-34960 | biostudies-arrayexpress

Determinants of H3K4me pattern establishment

Project description:A hallmark of genes transcribed by RNA polymerase II (RNApII) is a "gradient" of histone H3 lysine 4 (H3K4) methylation. Various factors differentially bind to H3K4me3 near promoters, H3K4me2 just downstream, and H3K4me1 further downstream to modulate gene expression. Set1/COMPASS, the single S. cerevisiae H3K4 methyltransferase, binds transcribing RNApII, but COMPASS may also be allosterically regulated by specific subunits and histone H2B ubiquitylation. To ask whether differential H3K4 methylation is determined by regulated activity at specific gene locations or by the amount of time COMPASS spends near the nucleosome, ChIP-Seq analyses was performed in cells with altered transcription elongation rates or with Set1 fused to RNApII. Our results support a simple model where higher H3K4 methylations result from both increased duration and frequency of COMPASS proximity to the nucleosome.

2017-11-12 | GSE95356 | GEO

Role of Histone Ubiquitylation and Deubiquitylation as Determined by the Analysis of an HTB1_K123R S. cerevisiae Strain

Project description:In Saccharomyces cerevisiae histone H2B is ubiquitylated at lysine 123. The SAGA complex component, Ubp8, is one of two proteases that remove this ubiquitin moiety. We analyzed gene expression in a strain containing a variant of histone H2B with lysine 123 converted to arginine to address the mechanisms by which ubiquitylation and deubiquitylation of histone H2B affects gene expression. We show that changes in gene expression observed upon deletion of ubp8 are suppressed by htb1K123R. This provides genetic evidence that Ubp8 alters gene expression through deubiquitylation of histone H2B. Second, microarray analyses of the htb1K123R strain show that loss of histone ubiquitylation results in a two-fold or greater change in expression of ~1.5% of the protein coding genes with greater than two-thirds increasing. For genes in which ubiquitylation represses expression, ubiquitylation principally acts through its effects on histone methylation. In contrast, decreased expression of the CWP1 gene was not paralleled by deletions of the methyltransferase components Swd3, Set2 or Dot1 and is thus likely independent of methylation. Finally, by comparing gene expression changes in the htb1K123R strain with those in a strain deleted for rad6, we conclude that lysine 123 affects transcription primarily because of its being a site of ubiquitylation. Keywords: yeast, histone ubiquitylation, Ubp8, gene expression, genetic modification, histone H2B Two dye-swapped, biological replicate experiments were performed for yeast strains CY1272(Htb1_K123R;htb2_delta0), BY10809(ubp8_delta0) and CY1383(Htb1_K123R;htb2_delta0;ubp8_delta0) with reference to BY4742(wt). Three biological replicates, including one dye-swap experiment, were performed comparing CY1272(Htb1_K123R;htb2_delta0) to BY13026(htb2_delta0).

2010-09-15 | E-GEOD-6316 | biostudies-arrayexpress

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