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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 31, 2012 |
| Title |
Genome-wide profiling of LXR, RXR and PPARα in mouse liver reveals extensive sharing of binding sites |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice is dependent on LXR and correlates with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the role of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily increases the genomic binding of RXR, whereas the LXR agonist T0901317 greatly increases both LXR and RXR binding. Functional annotation of putative direct LXR target genes revealed a significant association with classical LXR-regulated pathways as well as PPAR signaling pathways, and subsequent ChIP-seq mapping of PPARα binding demonstrated binding of PPARα to 71-88% of the identified LXR:RXR binding sites. Sequence analysis of shared binding regions combined with sequential ChIP on selected sites indicate that LXR:RXR and PPARα:RXR bind to degenerate response elements in a mutually exclusive manner. Together our findings suggest extensive and unexpected cross-talk between hepatic LXR and PPARα at the level of binding to shared genomic sites
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| Overall design |
LXR, RXR, PPARalpha and RNA Polymerase II ChIP-seq on livers from female C57BL/6 wild-type and/or LXRα/β-deficient mice (13 weeks of age, n=1) treated by oral gavage once daily for 14 days with the RXR agonist bexarotene (100 mg/kg body weight [mpk], in 1% carboxymethylcellulose), the LXR agonist T0901317 (T09, 30 mpk) or vehicle alone.
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| Contributor(s) |
Boergesen M, Gross B, van Heeringen SJ, Hagenbeek D, Bindesbøll C, Caron S, Lalloyer F, Steffensen KR, Nebb HI, Gustafsson J, Stunnenberg HG, Staels B, Mandrup S |
| Citation(s) |
22158963 |
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| Submission date |
Jan 23, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Susanne Mandrup |
| E-mail(s) |
s.mandrup@bmb.sdu.dk
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| Phone |
+45 6550 2340
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| Organization name |
University of Southern Denmark
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| Department |
Biochemistry and Molecular Biology
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| Street address |
Campusvej 55
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| City |
Odense M |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (23)
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| Relations |
| SRA |
SRP010657 |
| BioProject |
PRJNA152837 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35262_RAW.tar |
995.4 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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