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 complex 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.

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References:

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