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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
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