Genome-wide maps of Set1 and H3K4me3 in budding yeast
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE115910 | GEO | 2019/05/02
REPOSITORIES: GEO
Similar Datasets
Project description:H3K4me3 is catalyzed by the Set1/MLL family of methyltransferases, whose function in catalyzing H3K4me3 is unique. Impaired function of Set1/MLL family members can lead to many abnormalities, such as bone and nerve defects, leukemia, and even death. Although the Set1 family plays an important regulatory role in various biological processes, it is still unclear how the Set1 protein itself is regulated and how protein levels are maintained. Due to the numerous homologues, complex composition, and high molecular weight of Set1 in higher organisms, especially humans, related research is greatly limited. In brewing yeast, Set1 is the only methyltransferase that catalyzes H3K4me3 and is highly conserved between species. Therefore, yeast is an ideal model for studying the functions and mechanisms of the Set1 family. In addition, Set1 protein plays an important role in regulating gene transcription, promoting telomere silencing, and maintaining cell lifespan. The Set1 family also plays an important regulatory role in the occurrence and development of various cancers.
2023-10-24 | PXD042010 | Pride
Project description:Prp45 is a budding yeast NineTeen-Complex associated factor, which plays a role in pre-mRNA splicing. Because its human ortholog, SNW1/SKIP, is known to functionally and physically interact with factors involved in transcription elongation and chromatin modifications, it was suggested to be one of the coupling factors which functionally connect splicing and transcription. To determine whether yeast Prp45 has this function as well we tested the genetic interactions between prp45(1-169) allele and deletions of histone modifiers and transcription elongation regulators. RNA-seq analysis was performed to address the changes in transcription and/or splicing in strains deleted in set1, a histone methyltransferase responsible for H3K4 methylation, and the corresponding prp45(1-169) set1 double mutant. Total RNA was isolated by combining phenol-chlorophorm extraction with MasterPure Yeast RNA Purification Kit (Epicentre). Ribodepletion, library preparation and sequencing were performed by BGI Genomics.
2024-08-30 | E-MTAB-5335 | biostudies-arrayexpress
Project description:Genome-wide maps of Set1 and H3K4me3 in budding yeast
| PRJNA476475 | ENA
Project description:The stimulation of trimethylation of histone H3 lysine 4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied with multiple mechanisms proposed for this form of histone crosstalk. Cps35/Swd2 within COMPASS is considered to bridge these processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation without interacting with Cps35/Swd2, and such crosstalk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we use biochemical, structural, in vivo, and 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 crosstalk. Furthermore, the apparent wild-type levels of H3K4 trimethylation (H3K4me3) in the 762-Set1 strain is due to rogue methylase activity of this mutant resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to gene bodies and intergenic regions. We have also performed detailed screens and identified yeast strains lacking H2Bub, but containing intact H2Bub enzymes, that have normal levels of H3K4me3, suggesting that ubiquitination may not directly stimulate COMPASS, but rather works in a context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the ubiquitination machinery and Cps35/Swd2 function to focus COMPASS’ H3K4me3 activity at promoter-proximal regions in a context dependent manner. ChIP-Seq for H3K4ME3 in S. cerevisie wild-type strains and strains expressing a truncated form of Set1: aa762-1080 Set1. H3K4ME3 ChIP-Seq was also compared for wild-type, leo1 knockout, and chd1 knockout strains
2014-01-09 | E-GEOD-53241 | biostudies-arrayexpress
Project description:The stimulation of trimethylation of histone H3 lysine 4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied with multiple mechanisms proposed for this form of histone crosstalk. Cps35/Swd2 within COMPASS is considered to bridge these processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation without interacting with Cps35/Swd2, and such crosstalk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we use biochemical, structural, in vivo, and 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 crosstalk. Furthermore, the apparent wild-type levels of H3K4 trimethylation (H3K4me3) in the 762-Set1 strain is due to rogue methylase activity of this mutant resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to gene bodies and intergenic regions. We have also performed detailed screens and identified yeast strains lacking H2Bub, but containing intact H2Bub enzymes, that have normal levels of H3K4me3, suggesting that ubiquitination may not directly stimulate COMPASS, but rather works in a context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the ubiquitination machinery and Cps35/Swd2 function to focus COMPASS’ H3K4me3 activity at promoter-proximal regions in a context dependent manner.
2014-01-09 | GSE53241 | GEO
Project description:Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2 and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. We investigated the genome-wide occupancy patterns of Rad6, Swd2 and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both 5’region and 3’region of genes, which are overlapped with its tightly bound two complexes, Set1 and CPF (Cleavage and Polyadenylation Factor), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5ʹ region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5’region was impared and rather increased in the 3’ region. This study highlights that catalytic activity of Rad6 is essential for all the ways of Swd2’s binding to the transcribed genes and Set1 redistributes the Swd2 to 5’region for accomplishments of H3K4me3 in the genome-wide level.
2024-04-21 | GSE234564 | GEO
Project description:The Set1 family of histone H3 lysine 4 (H3K4) methyltransferases is highly conserved from yeast to humans. Here we show that the Set1 complex (Set1C) directly binds RNA in vitro through the regions that comprise the double RNA recognition motifs (dRRM) and N-SET domain within Set1 and its subunit Spp1. To investigate the functional relevance of RNA binding, we performed UV RNA cross-linking (CRAC) for Set1 and RNA polymerase II in parallel with ChIP-seq experiments. Set1 binds nascent transcripts through its dRRM. RNA binding is important to define the appropriate topology of Set1C distribution along transcription units and correlates with the efficient deposition of the H3K4me3 mark. In addition, we uncovered that Set1 binds to different classes of RNAs to levels that largely exceed the levels of binding to the general population of transcripts, suggesting the Set1 persists on these RNAs after transcription. This class includes RNAs derived from SET1, Ty1 retrotransposons, specific transcription factors genes and snRNAs. We propose that Set1 modulates adaptive responses, as exemplified by the posttranscriptional inhibition of Ty1 retrotransposition.
2017-10-03 | GSE104485 | GEO
Project description:The Set1 family of histone H3 lysine 4 (H3K4) methyltransferases is highly conserved from yeast to humans. Here we show that the Set1 complex (Set1C) directly binds RNA in vitro through the regions that comprise the double RNA recognition motifs (dRRM) and N-SET domain within Set1 and its subunit Spp1. To investigate the functional relevance of RNA binding, we performed UV RNA cross-linking (CRAC) for Set1 and RNA polymerase II in parallel with ChIP-seq experiments. Set1 binds nascent transcripts through its dRRM. RNA binding is important to define the appropriate topology of Set1C distribution along transcription units and correlates with the efficient deposition of the H3K4me3 mark. In addition, we uncovered that Set1 binds to different classes of RNAs to levels that largely exceed the levels of binding to the general population of transcripts, suggesting the Set1 persists on these RNAs after transcription. This class includes RNAs derived from SET1, Ty1 retrotransposons, specific transcription factors genes and snRNAs. We propose that Set1 modulates adaptive responses, as exemplified by the posttranscriptional inhibition of Ty1 retrotransposition.
2017-10-03 | GSE104484 | GEO
Project description:The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to nonmethylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between C. elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex.
2019-09-27 | PXD015548 | Pride
Project description:Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double-strand break (DSB) formation that in budding yeast takes place in gene promoters and is promoted by histone H3K4 di/trimethylation. This histone modification is recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote DSB formation close to gene promoters. How Set1 complex- and Mer2- related functions of Spp1 are connected is not clear. Here, combining genome-wide localization analyses, biochemical approaches and the use of separation of function mutants, we show that Spp1 is present within two distinct complexes in meiotic cells, the Set1 and the Mer2 complexes. Disrupting the Spp1-Set1 interaction mildly decreases H3K4me3 levels and does not affect meiotic recombination initiation. Conversely, the Spp1-Mer2 interaction is required for normal meiotic recombination initiation, but dispensable for Set1 complex-mediated histone H3K4 methylation. Finally, we provide evidence that Spp1 preserves normal H3K4me3 levels independently of the Set1 complex. We propose a model where Spp1 works in three ways to promote recombination initiation: first by depositing histone H3K4 methylation (Set1 complex), next by “reading” and protecting histone H3K4 methylation, and finally by making the link with the chromosome axis (Mer2-Spp1 complex). This work deciphers the precise roles of Spp1 in meiotic recombination and opens perspectives to study its functions in other organisms where H3K4me3 is also present at recombination hotspots.
2017-11-30 | GSE102790 | GEO