Retanoic X Receptor gamma

The human retinoid X receptors (RXRs) are encoded by three distinct genes (RXRa, RXRb, and RXRy) and bind selectively and with high affinity to the vitamin A derivative, 9-cis-retinoic acid. RXRs are type-II nuclear hormone receptors that are largely localized to the nuclear compartment independent of ligand binding. Nuclear RXRs form heterodimers with nuclear hormone receptor subfamily 1 proteins, including thyroid hormone receptor, retinoic acid receptors, vitamin D receptor, peroxisome proliferator-activated receptors, liver X receptors and farnesoid X receptor (1). Since RXRs heterodimerize with multiple nuclear hormone receptors, they play a central role in transcriptional control of numerous hormonal signaling pathways by binding to cis-acting response elements in the promoter/enhancer region of target genes (2). RXRy expression, unlike that of RXRa and RXRb, is restricted largely to cardiac muscle, skeletal muscle, thyroid gland, and thyrotrope cells of the anterior pititary gland (3-6). It is posited that RXRy plays a pivitol role in the transcriptional control of skeletal muscle differentiation as RXRy has been found to be directly associated with the promoter regions of MyoD and myogenin (7-10). RXRy is also involved in the transcriptional control of the hypothalamic-pituitary-thyroid axis through repression of the TSHb promoter (11-13).