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| Status |
Public on Oct 30, 2019 |
| Title |
Disruption of cardiac Med1 inhibits RNA polymerase-II promoter occupancy and induces chromatin remodeling |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
ChIP-sequencing data of RNA Pol-II, acetylated H3K27, and tri-metylated H3K27 from hearts of Med1 floxed and cardiac knockout mice.
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| Contributor(s) |
Hall DD, Spitler KM, Grueter CE |
| Citation(s) |
30461303 |
| |
| Submission date |
Aug 23, 2018 |
| Last update date |
Nov 01, 2019 |
| Contact name |
Duane Hall |
| E-mail(s) |
duane-hall@uiowa.edu
|
| Organization name |
University of Iowa
|
| Department |
Internal Medicine
|
| Lab |
2269 CBRB
|
| Street address |
285 Newton Rd
|
| City |
Iowa City |
| State/province |
IA |
| ZIP/Postal code |
52242 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA487584 |
| SRA |
SRP158681 |
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