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

Accession Number: E-GEOD-58680

Link to Dataset: http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-58680/

Repository: ArrayExpress

Data Type(s): Gene Expression

Experiment Type(s): ChIP-seq

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. Identification of BRD2, BRD3, BRD4, PolII, PolIIs2p and PolIIs5p binding sites in human stellate LX2 cells that were treated with DMSO (0.1 ) or JQ1 (500nM) for 16 hrs.

Publication(s) associated with this dataset:

• Ding N, Hah N, Yu RT, Sherman MH, Benner CW, Leblanc M, He M, Liddle C, Downes M, Evans RM. 2015. BRD4 is a novel therapeutic target for liver fibrosis. Proc Natl Acad Sci U S A 112(51):15713-15718. doi:10.1073/pnas.1522163112 PMID:26644586 PMCID:PMC4697417