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Series GSE118965 Query DataSets for GSE118965
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.
Overall design ChIP-sequencing data of RNA Pol-II, acetylated H3K27, and tri-metylated H3K27 from hearts of Med1 floxed and cardiac knockout mice.
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
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
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (7)
GSM3355003 Med1 fl/fl Pol-II ChIP
GSM3355004 Med1 cKO Pol-II ChIP
GSM3355005 Med1 fl/fl K27ac ChIP
BioProject PRJNA487584
SRA SRP158681

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Supplementary file Size Download File type/resource
GSE118965_RAW.tar 3.9 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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