Genome-wide Binding Potential and Regulatory Activity of the Glucocorticoid Receptor’s Monomeric and Dimeric Forms
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA482932 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10156681_1.fastq.gz | Fastqsanger.gz | |||
| SRR10156681_2.fastq.gz | Fastqsanger.gz | |||
| SRR10156682_1.fastq.gz | Fastqsanger.gz | |||
| SRR10156682_2.fastq.gz | Fastqsanger.gz | |||
| SRR10156683_1.fastq.gz | Fastqsanger.gz |
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Project description:A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.
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