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| Status |
Public on Dec 11, 2015 |
| Title |
Super-Enhancer-mediated Control of Liver Fibrosis by BET Bromodomain Proteins |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| Overall design |
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.
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| Contributor(s) |
Yu RT, Ding N, Evans RM |
| Citation(s) |
26644586 |
| Submission date |
Jun 19, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ruth T Yu |
| Organization name |
Salk Institute
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| Department |
Gene Expression Lab
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| Lab |
Ronald Evans
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| Street address |
10010 N Torrey Pines Rd
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA253142 |
| SRA |
SRP043435 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58680_RAW.tar |
413.0 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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