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Dataset Details

Superfund Research Program

Title: Super-Enhancer-mediated Control of Liver Fibrosis by BET Bromodomain Proteins

Accession Number: GSE58680

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58680

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Genome binding/occupancy profiling by high throughput sequencing

Organism(s): Homo sapiens

Summary: Here, we investigate the role of enhancers in myofibroblasts, a cell type that dominates the pathogenesis and progression of tissue fibrosis. We reveal that bromodomain and extra-terminal family members (BETs), an important group of epigenetic readers, are critical for super-enhancer-mediated pro-fibrotic gene expression in hepatic stellate cells (HSCs, lipid-containing liver-specific pericytes), upon activation during liver fibrogenesis give rise to myofibroblasts2-4. We observe significantly enriched localization of BETs to hundreds of super-enhancers associated with genes involved in multiple pro-fibrotic pathways. This unique loading pattern consequentially serves as a molecular mechanism by which BETs modulate pro-fibrotic gene expression in myofibroblasts. Strikingly, suppression of BET-enhancer interaction using small-molecule inhibitors such as JQ1 dramatically blocks activation of HSCs into myofibroblasts and significantly compromises the proliferation of activated HSCs.

Publication(s) associated with this dataset: Project(s) associated with this dataset:
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