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Transcription Activation by Nuclear Receptors

sigma-aldrich.com/cellsignaling

Transcription Activation by Nuclear Receptors

• Retinoid X receptor (RXR) and Retinoic Acid receptor (RAR) are nuclear receptors that bind either all trans-retinoic (tRA) or 9-cis-retinoic acid (9-cis-RA). In the absence of ligand, corepressors, such as Nuclear Receptor Corepressor (NCoR), Silencing Mediator of Retinoid and Thyroid Hormone Receptor (SMRT), and Histone Deacetylase-1 (HDAC-1) associate with the RAR:RXR heterodimer complex and repress transcription. The histone deacetylase activity of the complex helps maintain tight association between the deacetylated histones and chromatin that results in this repression.

sigma-aldrich.com/cellsignaling

Transcription Activation by Nuclear Receptors

sigma-aldrich.com/cellsignaling

Transcription Activation by Nuclear Receptors

• When tRA or 9-cis-RA binds to the RAR:RXR complex, a conformational change in the receptors causes the dissociation of the corepressors and subsequent recruitment and binding of coactivators such as Steroid Receptor Coactivator-1 (SRC-1), Glucocorticoid Receptor Interacting Protein-1 (GRIP-1), CREB Binding Protein (CBP) and CBP-Associated Factor (PCAF). This receptor:coactivator complex activates histone acetyltransferase (HAT). Acetylated histones dissociate from the chromatin and allow for the basal transcription machinery complex to bind to DNA and activate transcription of target genes.