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Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes.

Authors :
Wang H
Duan A
Zhang J
Wang Q
Xing Y
Qin Z
Liu Z
Yang J
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.

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