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Series GSE100889 Query DataSets for GSE100889
Status Public on Jul 07, 2017
Title Extensive overlap of the STAT6 and RXR cistromes in the active enhancer repertoire of human CD14+ monocyte-derived differentiating macrophages
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) g or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via multiple members of the nuclear hormone receptor family, including the retinoid X receptors (RXR). It has been also documented that cytokines are able to modulate macrophage responses to lipid signals but the nature of these interactions and the underlying mechanisms of these processes especially at the level of the chromatinized genome are not well understood. Previous work from our laboratory suggested that STAT6 is a facilitator of nuclear receptor mediated transcriptional activity acting at the genome level. This prompted us to investigate genome-wide DNA binding events and the development of cistromes in human CD14+ monocyte-derived macrophages upon exposure to IL-4. We determined the impact of IL-4 on the PU.1, RXR and STAT6 cistromes within the active enhancer regions marked by H3K27-acetylation using chromatin immunoprecipitation followed by deep sequencing and integrated bioinformatics analyses. We found that about 2/3rd of the IL-4 induced STAT6 peaks co-localized with RXR peaks. These STAT6/RXR co-peaks differed at least in part from the non-overlapping RXR peaks regarding the most enriched de novo transcription factor binding motifs. Interestingly, RXR-binding was not regulated at the STAT6/RXR co-bound enhancers following IL-4 stimulation, but differential enhancer interactions were observed between the IL-4/STAT6 and RXR signaling pathways acting in a gene selective manner. Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages.
Overall design RNA-seq and ChIP-seq-based characterization of the interaction between IL-4/STAT6 and RXR signaling pathways in differentiating human macrophages
Contributor(s) Nagy G, Nagy L
Citation(s) 28774779
BioProject PRJNA379060
Submission date Jul 06, 2017
Last update date Jul 25, 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)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (18)
GSM2695648 H3K27ac ChIP-seq analysis of untreated human differentiating macrophages
GSM2695649 H3K27ac ChIP-seq analysis of human differentiating macrophages treated with IL-4
GSM2695650 PU.1 ChIP-seq analysis of untreated human differentiating macrophages (rep1)
SRA SRP101844

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Supplementary file Size Download File type/resource
GSE100889_RAW.tar 21.6 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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