Physical and functional interaction between the SET1/COMPASS complex component CFP-1/CXXC and a Sin3S HDAC complex
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PROVIDER: PRJNA472359 | ENA |
REPOSITORIES: ENA
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Project description:The CFP1/CXXC protein targets SET1/COMPASS complexes to non-methylated CpG rich promoter regions to implement tri-methylation of histone H3 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context. Little is known about how CFP1 binding is coordinated with other chromatin factors. Using a proteomics approach, we establish a link between C. elegans CFP1 and a small Rpd3/Sin3 histone deacetylase (HDAC) complex (Sin3S). Mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate the expression of common genes. CFP-1 directly interacts with SIN-3 through a region including the conserved PAH1 domain, and contributes to recruitment of SIN-3 and the Sin3S subunit HDA-1 to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3 HDAC small complex at promoters, with implications for the coordinate regulation of gene expression by chromatin- associated complexes with distinct activities.
2019-09-29 | GSE114715 | 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:The highly conserved CFP1 CXXC zinc finger protein targets SET1 family complexes to promoter regions to implement methylation of histone H3 Ly4 (H3K4me), a mark that correlates with gene expression depending on the chromatin context. Whether CFP1 physically interacts with additional chromatin modifying proteins on chromatin has not been investigated. By applying interaction proteomics coupled to mass spectrometry to identify factors that interact with C. elegans CFP-1, we establish a link between CFP-1 and the Rpd3/Sin3 histone deacetylase (HDAC) small complex (Rpd3/Sin3S) in embryos. We show that CFP-1 directly interacts with SIN-3 through a highly conserved C-terminal domain, and that the two proteins extensively colocalize with H3K4me3 at promoter regions genome-wide. Animals lacking sin-3, cfp-1 or the catalytic H3K4 methyltransferase subunit set-2/SET1 show misregulation of common genes in early embryos, reduction in fertility, and defects in the division of intestinal cells in adults, consistent with common developmental functions. Our results suggest that in addition to its well characterized role as a central subunit of the SET-2/SET1 complex, CFP-1 interacts with the Sin3S/HDAC complex at promoter regions to influence gene expression in a developmental context. This has implications for the coordinate regulation of gene expression by chromatin associated complexes with distinct activities.
2019-09-26 | GSE110072 | GEO
Project description:Changes in histone post-translational modifications are associated with aging through poorly defined mechanisms. Histone 3 lysine 4 (H3K4) methylation at promoters is deposited by SET1 family methyltransferases acting within conserved multiprotein complexes known as COMPASS. Using co-immunopurification coupled to mass spectrometry-based proteomics, we characterized complex members and binding partners in various genetic contexts, using WDR-5 or CFP-1 proteins as baits.
2021-12-08 | PXD029904 | Pride
Project description:Physical and functional interaction between the SET1 complex component CFP-1/CXXC and the Sin-3S/HDAC complex in C. elegans embryos
| PRJNA432698 | 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:H3K4 methylation is a conserved histone modification crucial for gene regulation, yet the post-translational modifications of the Set1-COMPASS complex remain largely unexplored. This study elucidates the significance of N-terminal acetylation in modulating H3K4 methylation patterns. Firstly, loss of NatA complex resulted in a significant decrease in H3K4me3 levels and a shift of H3K4me2 from 5' transcribed regions to promoters. Importantly, NatA physically interacted with the Set1-COMPASS complex and facilitated N-terminal acetylation of the Shg1 subunit. Surprisingly, deletion of SHG1 or mutation of the acetylation site (A2P) in Shg1 led to reduced H3K4 methylation in cells lacking Spp1. Additionally, NatB complex also contributed to H3K4 methylation regulation, potentially through N-terminal acetylation of Swd1. These findings highlight the novel role of N-terminal acetylation in fine-tuning the function of the Set1-COMPASS complex and shaping H3K4 methylation patterns. This study sheds light on the intricate regulation of H3K4 methylation and emphasizes the significance of N-terminal acetylation as a regulatory mechanism in this process.
2024-05-31 | GSE253436 | GEO
Project description:TET proteins convert 5-methylcytosine to 5-hydroxymethylcytosine, an emerging dynamic epigenetic state of DNA that can influence transcription. Evidence has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited. Here, we show a direct interaction of TET2 and TET3 with O-GlcNAc transferase (OGT). OGT does not appear to influence hmC activity, rather TET2 and TET3 promote OGT activity. TET2/3-OGT co-localize on chromatin at active promoters enriched for H3K4me3 and reduction of either TET2/3 or OGT activity results in a direct decrease in H3K4me3 and concomitant decreased transcription. Further, we show that Host Cell Factor 1 (HCF1), a component of the H3K4 methyltransferase SET1/COMPASS complex, is a specific GlcNAcylation target of TET2/3-OGT, and modification of HCF1 is important for the integrity of SET1/COMPASS. Additionally, we find both TET proteins and OGT activity promote binding of the SET1/COMPASS H3K4 methyltransferase, SETD1A, to chromatin. Finally, studies in Tet2 knockout mouse bone marrow tissue extend and support the data as decreases are observed of global GlcNAcylation and also of H3K4me3, notably at several key regulators of haematopoiesis. Together, our results unveil a step-wise model, involving TET-OGT interactions, promotion of GlcNAcylation, and influence on H3K4me3 via SET1/COMPASS, highlighting a novel means by which TETs may induce transcriptional activation. ChIP-Seq experiments were performed on Illumina HiScanSQ sequencer in wild-type HEK293T cells for H3K4me3 histone marks, O-GlcNAc and HCF1, for HT-TET2, HT-TET3 and HT-OGT in HEK293T cells overexpressing those three fusion proteins and in TET2 Kd HEK293T cells for H3K4me3 histone marks. ChIP-Seqs were also performed in mouse bone marrow tissues for H3K4me3 histone marks, O-GlcNAc, endogenous Tet2 and in Tet2 Ko bone marrow tissues for H3K4me3 histone marks.
2013-02-07 | E-GEOD-36620 | biostudies-arrayexpress
Project description:Methylation of histone H3 lysine 4 (H3K4) by the Set1/COMPASS complex is coupled with active transcription, and this modification is important for regulating gene expression. Set1/COMPASS associates with the RNA polymerase II (RNApII) C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations.To ask how the Set1-RNApII CTD binding affects the occupancy and overall level of H3K4 methylations, ChIP-Seq was pefromed in cells transformed with full length or N-terminal truncated Set1. Our results indicate that Set1-RNApII CTD interaction is necessary for maintaining H3K4 methylations throughout the genes.
2019-10-02 | GSE138281 | GEO
Project description:Genome-wide analysis of the role of Histone 3 lysine 4 methylation in S. cerevisiae transcription by analyzing different mutants of the Set1/Compass complex, under steady-state and dynamic conditions
2011-02-18 | E-TABM-486 | biostudies-arrayexpress