Yeast Swd2 Is Essential Because of Antagonism between Set1 Histone Methyltransferase Complex and APT (Associated with Pta1) Termination Factor

Soares, Luis M.; Buratowski, Stephen

doi:10.1074/jbc.m112.341412

Cited by 48 publications

(53 citation statements)

References 62 publications

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“…COMPASS consists of seven additional subunits that promote complex integrity (Swd1, Swd2, Swd3, Bre2), regulate catalytic activity (Sdc1 and Spp1), or have unknown function (Shg1) (Takahashi and Shilatifard 2010;Mersman et al 2011;Takahashi et al 2011). Unlike other COMPASS members, Swd2 also functions as part of the APT transcription termination complex, and its role in this complex is essential for cell viability (Soares and Buratowski 2012). For this reason, Swd2 was not included in our screen.…”

Section: Resultsmentioning

confidence: 99%

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

et al. 2012

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DNA replication is a highly regulated process that is initiated from replication origins, but the elements of chromatin structure that contribute to origin activity have not been fully elucidated. To identify histone post-translational modifications important for DNA replication, we initiated a genetic screen to identify interactions between genes encoding chromatin-modifying enzymes and those encoding proteins required for origin function in the budding yeast Saccharomyces cerevisiae. We found that enzymes required for histone H3K4 methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase Bre1, are required for robust growth of several hypomorphic replication mutants, including cdc6-1. Consistent with a role for these enzymes in DNA replication, we found that both Set1 and Bre1 are required for efficient minichromosome maintenance. These phenotypes are recapitulated in yeast strains bearing mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains lacking specific COMPASS complex members or containing H2B mutations that differentially affect H3K4 methylation states, we determined that these replication defects were due to loss of H3K4 di-methylation. Furthermore, histone H3K4 di-methylation is enriched at chromosomal origins. These data suggest that H3K4 di-methylation is necessary and sufficient for normal origin function. We propose that histone H3K4 di-methylation functions in concert with other histone posttranslational modifications to support robust genome duplication. DNA replication initiates at discrete genomic loci termed "origins of replication." Each eukaryotic chromosome is replicated from many individual origins to ensure complete and precise genome duplication during each cell division cycle. Individual origins vary both in the likelihood that they will initiate replication, or "fire," in any given S phase and in the firing time within the S phase (Weinreich et al. 2004). Highly efficient origins fire in most cell cycles, whereas inefficient origins fire in only some cycles and are usually passively replicated by forks emanating from neighboring efficient origins. Although highly efficient origins that support initiation in most cell cycles have been identified in many genomes, the chromosomal determinants of origin location and function are still incompletely understood. Strikingly, while DNA sequence elements can be necessary, it is clear that sequence alone is insufficient to fully specify eukaryotic origin location and activity (Méchali 2010).Like all DNA-templated processes, replication occurs on chromatin. Recent progress in the field has demonstrated that the chromatin structure surrounding origins plays an essential role in controlling origin activity. For example, the positioning of nucleosomes near origins can either stimulate or inhibit origin function (Simpson 1990;Crampton et al. 2008;Berbenetz et al. 2010;Eaton et al. 2010). The major protein compon...

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Section: Resultsmentioning

confidence: 99%

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

et al. 2012

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“…COMPASS is composed of seven subunits in addition to Set1, which, ordered by molecular weight, are Cps60/Bre2, Cps50/ Swd1, Cps40/Spp1, Cpd35/Swd2, Cps30/Swd3, Cps25/ Sdc1, and Cps15/Shg1 (Miller et al 2001). Three independent groups have demonstrated a connection between the Cps35/Swd2 subunit of COMPASS and its interaction with monoubiquitinated chromatin and cross-talk to H3K4me3 (Lee et al 2007;Zheng et al 2010;Soares and Buratowski 2012). In the absence of the Rad6 or Bre1 ubiquitin ligase or in strains bearing the K123R mutant form of H2B, Cps35/Swd2 is not properly recruited to chromatin (Lee et al 2007;Zheng et al 2010;Soares and Buratowski 2012).…”

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confidence: 99%

“…Three independent groups have demonstrated a connection between the Cps35/Swd2 subunit of COMPASS and its interaction with monoubiquitinated chromatin and cross-talk to H3K4me3 (Lee et al 2007;Zheng et al 2010;Soares and Buratowski 2012). In the absence of the Rad6 or Bre1 ubiquitin ligase or in strains bearing the K123R mutant form of H2B, Cps35/Swd2 is not properly recruited to chromatin (Lee et al 2007;Zheng et al 2010;Soares and Buratowski 2012). Furthermore, Cps35/Swd2's association with COMPASS was reduced threefold in yeast mutants lacking H2Bub (Lee et al 2007;Zheng et al 2010).…”

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confidence: 99%

“…Furthermore, Cps35/Swd2's association with COMPASS was reduced threefold in yeast mutants lacking H2Bub (Lee et al 2007;Zheng et al 2010). However, Cps35/Swd2 is in at least one other complex in addition to COMPASS, and complicated genetic interactions between these complexes leave it unclear which are direct and which are indirect effects (Soares and Buratowski 2012).…”

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confidence: 99%

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Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation

et al. 2014

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The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner.

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“…The observation that Su(s) is less stable in the absence of Wdr82 is consistent with this idea. The yeast Wdr82 homolog, Sdw2, is required for recruitment of termination factors in the APT complex to snoRNA genes (Nedea et al 2003;Soares and Buratowski 2012). Furthermore, mammalian Wdr82 interacts directly with Pol II that is phosphorylated at Ser5 (Ser5P) CTD repeats (Lee and Skalnik 2008).…”

Section: Discussionmentioning

confidence: 99%

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

Brewer-Jensen

Wilson

Abernethy

et al. 2015

RNA

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Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism.

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Yeast Swd2 Is Essential Because of Antagonism between Set1 Histone Methyltransferase Complex and APT (Associated with Pta1) Termination Factor

Cited by 48 publications

References 62 publications

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

DNA Replication Origin Function Is Promoted by H3K4 Di-methylation inSaccharomyces cerevisiae

Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

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