The Corepressor CTBP2 is a Coactivator of Retinoic Acid Receptor/retinoid X Receptor in Retinoic Acid Signaling

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2013 Jun 19

PMID 23775127

Citations 13

Authors

Prashanth Kumar Bajpe

Guus J J E Heynen

Lorenza Mittempergher

Wipawadee Grernrum

Iris A de Rink

Wouter Nijkamp

Roderick L Beijersbergen

Rene Bernards

Sidong Huang

Affiliations

Soon will be listed here.

Abstract

Retinoids play key roles in development, differentiation, and homeostasis through regulation of specific target genes by the retinoic acid receptor/retinoid X receptor (RAR/RXR) nuclear receptor complex. Corepressors and coactivators contribute to its transcriptional control by creating the appropriate chromatin environment, but the precise composition of these nuclear receptor complexes remains to be elucidated. Using an RNA interference-based genetic screen in mouse F9 cells, we identified the transcriptional corepressor CTBP2 (C-terminal binding protein 2) as a coactivator critically required for retinoic acid (RA)-induced transcription. CTBP2 suppression by RNA interference confers resistance to RA-induced differentiation in diverse murine and human cells. Mechanistically, we find that CTBP2 associates with RAR/RXR at RA target gene promoters and is essential for their transactivation in response to RA. We show that CTBP2 is indispensable to create a chromatin environment conducive for RAR/RXR-mediated transcription by recruiting the histone acetyltransferase p300. Our data reveal an unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXR in RA signaling.

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