Physical and functional interaction between the SET1 complex component CFP-1/CXXC and the Sin-3S/HDAC complex in C. elegans embryos
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ABSTRACT:
PROVIDER: PRJNA432698 | ENA |
REPOSITORIES: ENA
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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: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:Physical and functional interaction between the SET1/COMPASS complex component CFP-1/CXXC and a Sin3S HDAC complex
| PRJNA472359 | ENA
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:W614A-3S peptide is a modified 3S motif of the HIV-gp41 (mutation W614A). We previously detected the presence of natural neutralizing antibodies directed against W614A-3S peptide (NAbs) in long-term non-progressor HIV+ patients. Here, we compared the efficacy of W614A-3S peptide formulated in either squalene emulsion (SQE) or in aluminum hydroxide (Alum) in inducing broadly-NAbs (bNAbs). Rabbit and mouse models were used to screen the induction of bNAbs following 4 immunizations. SQE was more efficient than Alum formulation in inducing W614A-3S-specific bNAbs with up to 67-93% of HIV strains neutralized. We then analyzed the quality of peptide-specific murine B cells by single-cell gene expression by quantitative Reverse Transcription-PCR and single-cell V(D)J sequencing. We found more frequent germinal center B cells in SQE than in Alum, albeit with a different gene expression profile. The V(D)J sequencing of W614A-3S-specific BCR showed significant differences in BCR sequences and validates the dichotomy between adjuvant formulations. All sixteen BCR sequences which were cloned were specific of peptide. Adjuvant formulations of W614A-3S-peptide-conjugated immunogen impact the quantity and quality of B cell immune responses at both the gene expression level and BCR sequence. We used a single-cell quantitative Reverse Transcription-PCR (qRT-PCR) approach to compare between the two formulations the quality of W614A-3S-specific B cell populations isolated from draining lymph nodes, one week after 2nd and 3rd immunizations (W3 and W5, respectively).
2022-03-19 | GSE198952 | GEO
Project description:Vibrio cholerae is a Gram negative, motile, facultative anaerobic bacterium, and the causative agent of cholera, a severe diarrhoeal disease, which untreated can rapidly lead to dehydration, hypotensive shock, and death. Cholera is a significant human disease that is estimated to affect 3-5 million people each year. The mechanism by which V. cholerae regulates virulence gene expression in vivo is unknown, but a number of studies have suggested that low molecular weight signally molecules may be important in modulating gene expression. cFP is a low molecular weight cyclic dipeptide produced by multiple Vibrio species. Evidence previously generated in our laboratory showed that cFP inhibited the production of the virulence factors cholera toxin (CT) and the toxin coregulated pilus (TCP) in O1 El Tor V. cholerae strain N16961 during growth under virulence gene inducing conditions. cFP inhibition of CT and TCP production correlated with reduced transcription of several regulators that belong to the ToxR regulon. To identify additional cFP-responsive genes we performed microarray experiments with the O1 El Tor V. cholerae strain N16961. In these experiments N16961 was grown under virulence gene inducing conditions in the presence and absence of cFP before RNA was extracted and hybridized to microarrays. The results showed that cFP positively affected the expression of the LysR-family regulatory protein LeuO. This finding suggests the possibility that LeuO may be mediating cFP-dependent regulation of gene expression in response to environmental cFP. V. cholerae N16961 was grown under AKI growth condition in the presence or absence of 1 mM cFP for 2.5 or 3 hours when total RNA was extracted, differentially labelled and hybridized to microarrays. Four independent experiments were performed.
2013-08-13 | E-GEOD-38272 | biostudies-arrayexpress
Project description:Vibrio cholerae is a Gram negative, motile, facultative anaerobic bacterium, and the causative agent of cholera, a severe diarrhoeal disease, which untreated can rapidly lead to dehydration, hypotensive shock, and death. Cholera is a significant human disease that is estimated to affect 3-5 million people each year. The mechanism by which V. cholerae regulates virulence gene expression in vivo is unknown, but a number of studies have suggested that low molecular weight signally molecules may be important in modulating gene expression. cFP is a low molecular weight cyclic dipeptide produced by multiple Vibrio species. Evidence previously generated in our laboratory showed that cFP inhibited the production of the virulence factors cholera toxin (CT) and the toxin coregulated pilus (TCP) in O1 El Tor V. cholerae strain N16961 during growth under virulence gene inducing conditions. cFP inhibition of CT and TCP production correlated with reduced transcription of several regulators that belong to the ToxR regulon. To identify additional cFP-responsive genes we performed microarray experiments with the O1 El Tor V. cholerae strain N16961. In these experiments N16961 was grown under virulence gene inducing conditions in the presence and absence of cFP before RNA was extracted and hybridized to microarrays. The results showed that cFP positively affected the expression of the LysR-family regulatory protein LeuO. This finding suggests the possibility that LeuO may be mediating cFP-dependent regulation of gene expression in response to environmental cFP.
2013-08-13 | GSE38272 | GEO
Project description:Bacillus bacteriophage vB_BceS_KLEB30-3S genome sequencing
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Project description:The TET3 CXXC domain has unique DNA binding properties. It binds to DNA in a cytosine-dependent manner that prefers binding to CpG dinucleotides but is not restricted by the CpG-content, distinct from other well-characterized CXXC domains. To map the TET3 CXXC domain binding sites across the human genome, we purified the GST-tagged TET3 CXXC domain protein and performed the GST pull-down assay using the genomic DNA purified from HEK293T cells. The enriched DNA fragments were then sequenced and aligned to human genome(hg19). We used the GST pull-down assay followed by DNA deep sequencing to map the DNA bound by the TET3 CXXC domain in vitro.
2012-12-10 | E-GEOD-41551 | biostudies-arrayexpress
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