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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 16, 2023 |
| Title |
Pioneer factor Foxa2 mediates chromatin conformation changes in ligand-dependent activation of nuclear receptor FXR |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Activation of nuclear receptors, a family of ligand-dependent transcription factors, is used extensively in development of drug targets. We have previously shown that pioneer factor Foxa2 opens chromatin for binding of nuclear receptors FXR and LXRα during acute ligand activation. FXR is activated by bile acids and deletion of Foxa2 in the liver results in intrahepatic cholestasis. We hypothesized that Foxa2 also enables chromatin conformational changes during ligand activation. We performed Foxa2 HiChIP to assess Foxa2-dependent long-range interactions in mouse livers treated with either vehicle control or FXR agonist GW4064. HiChIP contact analysis shows that global chromatin interactions are dramatically increased during FXR activation. Ligand-treated livers exhibit extensive redistribution of topological associated domains (TAD) and substantial increase in Foxa2-anchored loops, suggesting Foxa2 is involved in dynamic chromatin conformational changes. We demonstrate that chromatin conformation, including genome-wide interactions, TADs, intra-chromosomal and inter-chromosomal Foxa2-anchored loops, drastically changes upon addition of FXR agonist. Hence, we determine a novel role for Foxa2 in enabling these conformational changes, extending its function in bile acid metabolism.
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| Overall design |
Foxa2 HiChIP-Seq (Hi-C & Foxa2 ChiP) in mouse livers treated with vehicle or FXR agonist GW4064
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| Contributor(s) |
Bochkis IM, Hao Y, Han L, Wu A |
| Citation(s) |
37879405 |
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| Submission date |
Apr 05, 2023 |
| Last update date |
Jan 15, 2024 |
| Contact name |
Irina Bochkis |
| E-mail(s) |
imb3q@virginia.edu
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| Organization name |
University of Virginia
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| Department |
Pharmacology
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| Lab |
Bochkis
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| Street address |
1340 Jefferson Park Ave Jordon Hall 5030
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA952640 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229049_RAW.tar |
73.1 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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