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Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes.
- Source :
-
Communications biology [Commun Biol] 2021 Jun 03; Vol. 4 (1), pp. 675. Date of Electronic Publication: 2021 Jun 03. - Publication Year :
- 2021
-
Abstract
- Elucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.
- Subjects :
- A549 Cells
Binding Sites genetics
Cell Line
Cells, Cultured
Chromatin genetics
Chromatin Immunoprecipitation Sequencing methods
Glucocorticoids pharmacology
HeLa Cells
Humans
K562 Cells
MCF-7 Cells
Podocytes cytology
Podocytes drug effects
Protein Binding
Receptors, Glucocorticoid genetics
Regulatory Elements, Transcriptional genetics
Transcriptome genetics
Chromatin metabolism
Cytoskeleton metabolism
Podocytes metabolism
Receptors, Glucocorticoid metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 34083716
- Full Text :
- https://doi.org/10.1038/s42003-021-02209-8