Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Vitamin D-dependent recruitment of corepressors to vitamin D/retinoid X receptor heterodimers.

Sánchez-Martínez R, Zambrano A, Castillo AI, Aranda A

Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cieníficas and Universidad Autónoma de Madrid, Madrid, Spain.

Transcriptional regulation by nuclear receptors is mediated by recruitment of coactivators and corepressors. In the classical model, unliganded nonsteroidal receptors bind corepressors, such as the silencing mediator of thyroid and retinoid receptors (SMRT) or nuclear corepressor (NCoR), that are released upon ligand binding. We show here that, unlike other receptors, the heterodimer of the vitamin D receptor (VDR) with the retinoid X receptor (RXR) recruits NCoR and SMRT strictly in a VDR agonist-dependent manner. Binding of an agonist to VDR allows its partner receptor, RXR, to bind the corepressors. The RXR ligand has the opposite effect and induces corepressor release from the heterodimer. 1,25-Dihydroxy-vitamin D(3) (VD3) causes recruitment of SMRT and NCoR to a VDR target promoter. Down-regulation of corepressors by means of small interfering RNA enhances transcriptional responses to VD3. These data reveal a new paradigm of SMRT and NCoR binding to nuclear receptors and demonstrate that these corepressors can function as physiological negative regulators of VD3-mediated transcription.

Published 15 May 2008 in Mol Cell Biol, 28(11): 3817-29.
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