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| Status |
Public on Jan 01, 2018 |
| Title |
The IL-4/STAT6/PPARγ signaling axis is driving the expansion of the RXR heterodimer cistrome, providing complex ligand responsiveness in macrophages I |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting specific roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive. Here we show that IL-4-mediated macrophage plasticity results in a greatly extended RXR cistrome via the direct and indirect actions of the transcription factor STAT6. Activation of STAT6 leads to chromatin remodeling and RXR recruitment to de novo enhancers. In addition, STAT6 triggers a secondary transcription factor wave, including PPARγ. PPARγ appears to be indispensable for the development of RXR-bound de novo enhancers, whose activities can be modulated in a very restricted manner by the ligands of the PPARγ:RXR heterodimer. Collectively, these data reveal the mechanisms leading to the dynamic extension of the RXR cistrome, identify the lipid-sensing enhancer set of alternatively polarized macrophages and suggest a pervasive ligand-independent mechanism of action of the receptors.
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| |
|
| Overall design |
CTCF and RAD21 binding sites
|
| |
|
| Contributor(s) |
Nagy G, Nagy L |
| Citation(s) |
29506156, 34846534 |
| BioProject |
PRJNA194083 |
| Submission date |
Nov 28, 2017 |
| Last update date |
Dec 10, 2021 |
| Contact name |
Gergely Nagy |
| Organization name |
University of Debrecen
|
| Department |
Department of Biochemistry and Molecular Biology
|
| Street address |
Egyetem ter 1.
|
| City |
Debrecen |
| ZIP/Postal code |
4032 |
| Country |
Hungary |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (2) |
| GSM2867715 |
Genome-wide localization analyses of CTCF binding sites |
| GSM2867716 |
Genome-wide localization analyses of RAD21 binding sites |
|
| This SubSeries is part of SuperSeries: |
| GSE110465 |
The IL-4/STAT6/PPARγ signaling axis is driving the extension of the RXR heterodimer cistrome, providing complex ligand responsiveness in macrophages |
|
| Relations |
| SRA |
SRP019970 |
