Molecular and cellular biologyJun 19, 2013

The protein CTBP2 helps activate retinoic acid signaling by working with retinoic acid receptors

Updated Feb 27, 2026

Abstract

CTBP2 is identified as a critical coactivator for retinoic acid-induced transcription.

Retinoids regulate development and gene expression through the RAR/RXR nuclear receptor complex.
Corepressors and coactivators are involved in the transcriptional control of this complex.
Suppression of CTBP2 leads to resistance against differentiation induced by retinoic acid in various cell types.
CTBP2 interacts with RAR/RXR at the promoters of retinoic acid target genes, essential for their activation.
CTBP2 facilitates a chromatin environment that supports transcription by recruiting the histone acetyltransferase p300.
This study reveals an unexpected role of CTBP2 as a coactivator in retinoic acid signaling.

Simplified

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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