Disruption of cardiac Med1 inhibits RNA polymerase-II promoter occupancy and induces chromatin remodeling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA487584 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7747160.fastq.gz | Fastqsanger.gz | |||
| SRR7747161.fastq.gz | Fastqsanger.gz | |||
| SRR7747162.fastq.gz | Fastqsanger.gz | |||
| SRR7747163.fastq.gz | Fastqsanger.gz | |||
| SRR7747164.fastq.gz | Fastqsanger.gz |
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Project description:The Mediator co-activator complex directs gene specific expression by binding distal enhancer-bound transcription factors through its Med1 subunit while bridging to RNA Polymerase-II (Pol-II) at gene promoters. In addition, Mediator scaffolds epigenetic modifying enzymes that determine local DNA accessibility. We previously found that deletion of Med1 in cardiomyocytes deregulates more than 5000 genes and promotes acute heart failure and hypothesize Med1 deficiency disrupts enhancer-promoter coupling. Using ChIP-seq, we find Pol-II pausing index is increased in Med1 knockout versus floxed control hearts primarily from decreased Pol-II occupancy at the majority of transcriptional start sites. Med1-dependent gene expression correlates strongly with histone H3 K27 acetylation while H3 K27 tri-methylated levels are increased and inversely correlate with absolute expression levels. Furthermore, Med1 deletion leads to dynamic changes in acetyl-K27 associated super-enhancer regions and their enriched transcription factor binding motifs that are consistent with altered gene expression. Our findings suggest that Med1 is important in establishing enhancer-promoter coupling in the heart by facilitating the recruitment of Pol-II to gene promoters, determining chromatin accessibility within genes and enhancer regions and altering transcription factor binding motifs that are likely important in directing gene-specific expression.
2019-10-30 | GSE118965 | GEO
Project description:The Mediator coactivator complex directs gene-specific expression by binding distal enhancer-bound transcription factors through its Med1 subunit while bridging to RNA polymerase II (Pol II) at gene promoters. In addition, Mediator scaffolds epigenetic modifying enzymes that determine local DNA accessibility. Previously, we found that deletion of Med1 in cardiomyocytes deregulates more than 5,000 genes and promotes acute heart failure. Therefore, we hypothesized that Med1 deficiency disrupts enhancer-promoter coupling. Using chromatin immunoprecipitation-coupled deep sequencing (ChIP-seq; n = 3/ChIP assay), we found that the Pol II pausing index is increased in Med1 knockout versus floxed control mouse hearts primarily due to a decrease in Pol II occupancy at the majority of transcriptional start sites without a corresponding increase in elongating species. Parallel ChIP-seq assays reveal that Med1-dependent gene expression correlates strongly with histone H3 K27 acetylation, which is indicative of open and active chromatin at transcriptional start sites, whereas H3 K27 trimethylated levels, representing condensed and repressed DNA, are broadly increased and inversely correlate with absolute expression levels. Furthermore, Med1 deletion leads to dynamic changes in acetyl-K27 associated superenhancer regions and their enriched transcription factor-binding motifs that are consistent with altered gene expression. Our findings suggest that Med1 is important in establishing enhancer-promoter coupling in the heart and supports the proposed role of Mediator in establishing preinitiation complex formation. We also found that Med1 determines chromatin accessibility within genes and enhancer regions and propose that the composition of transcription factors associated with superenhancer changes to direct gene-specific expression. NEW & NOTEWORTHY Based on our previous findings that transcriptional homeostasis and cardiac function are disturbed by cardiomyocyte deletion of the Mediator coactivator Med1 subunit, we investigated potential underlying changes in RNA polymerase II localization and global chromatin accessibility. Using chromatin immunoprecipitation sequencing, we found that disrupted transcription arises from a deficit in RNA polymerase II recruitment to gene promoters. Furthermore, active versus repressive chromatin marks are redistributed within gene loci and at enhancer regions correlated with gene expression changes.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
2025-08-01 | GSE297932 | GEO
Project description:Chromatin occupancy of MED1 and other Mediator components, as well as Pol II, were studied in MCF7 cells. MED1 acetylation affects chromatin occupancy of its related factors, which was analyzed with CUT&RUN-seq, ChIP-seq and sequential ChIP-seq assay (by pan-acetyl-lysine antibody) with MED1 KR mutant (HA tag) where acetylation residues were replaced. Combined with RNA seq analysis for gene expression in MCF7 cells with MED1 KO and KR/KQ MED1 ectopic expression, the role of MED1 acetylation in gene transcription control was investigated.
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