Download No Slide Title

Hormonal Targeting of Nuclear Complexes to Chromatin
SIGMA-ALDRICH
Hormonal Targeting of Nuclear Complexes to Chromatin
In the absence of ligand, a silencing mediator of retinoid and thyroid hormone receptor
(SMRT)-mSin3a-histone deacetylase-1 (HDAC-1) complex associates with the nuclear
retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimeric complex. The HDAC
activity of the complex maintains the tight association between deacetylated histones and
chromatin that results in repressed gene transcription. When 9-cis retinoic acid binds to the
RAR-RXR heterodimeric complex the corepressor complex dissociates from the receptor
complex with simultaneous recruitment of a coactivator comple, that includes CREB-binding
protein (CBP), CBP-associated factor (p/CAF), and steroid receptor coactivator-1 (SRC-1).
The receptor/coactivator complex activates histone acetyltransferase (HAT). Acetylated
histone dissociates from the chromatin, allowing the preinitiation complex (PIC) to bind to
DNA and the ligand heterodimeric RAR-RXR-coactivator complex to bind to specific DNA
response elements (RARE) in the promoter regions of target genes to activate transcription.
References
Li, H., et al., Characterization of receptor interaction and transcriptional repression by the
corepressor SMRT. Mol. Endocrinol., 11, 2025-2037 (1997).
Blanco, J.C., et al., The histone acetylase PCAF is a nuclear receptor coactivator. Genes
Dev., 12, 1638-1651 (1998).
Minucci, S., et al., Retinoid receptors in health and disease: co-regulators and the chromatin
connection. Semin. Cell Dev. Biol., 10, 215-225.(1999).