BCOR modulates transcriptional activity of a subset of glucocorticoid receptor target genes involved in cell growth and mobility.

Autor: Manjur ABMK; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Lempiäinen JK; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Malinen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland., Varjosalo M; Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Palvimo JJ; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Niskanen EA; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: einari.niskanen@uef.fi.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2021 Jun; Vol. 210, pp. 105873. Date of Electronic Publication: 2021 Mar 17.
DOI: 10.1016/j.jsbmb.2021.105873
Abstrakt: Glucocorticoid (GC) receptor (GR) is a key transcription factor (TF) that regulates vital metabolic and anti-inflammatory processes. We have identified BCL6 corepressor (BCOR) as a dexamethasone-stimulated interaction partner of GR. BCOR is a component of non-canonical polycomb repressor complex 1.1 (ncPCR1.1) and linked to different developmental disorders and cancers, but the role of BCOR in GC signaling is poorly characterized. Here, using ChIP-seq we show that, GC induces genome-wide redistribution of BCOR chromatin binding towards GR-occupied enhancers in HEK293 cells. As assessed by RNA-seq, depletion of BCOR altered the expression of hundreds of GC-regulated genes, especially the ones linked to TNF signaling, GR signaling and cell migration pathways. Biotinylation-based proximity mapping revealed that GR and BCOR share several interacting partners, including nuclear receptor corepressor NCOR1. ChIP-seq showed that the NCOR1 co-occurs with both BCOR and GR on a subset of enhancers upon GC treatment. Simultaneous depletion of BCOR and NCOR1 influenced GR target gene expression in a combinatorial and gene-specific manner. Finally, we show using live cell imaging that the depletion of BCOR together with NCOR1 markedly enhances cell migration. Collectively, our data suggest BCOR as an important gene and pathway selective coregulator of GR transcriptional activity.
(Copyright © 2021. Published by Elsevier Ltd.)
Databáze: MEDLINE
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