Gene Activation by Thyroid Hormone Receptor In Vitro and Purification of the TRAP Coactivator Complex

Thyroid hormone receptors (TRs) are capable of both activating and repressing transcription from genes bearing TR-binding elements (TREs). In general, TRs function as activators in the presence of thyroid hormone (T3) and repressors in the absence of T3 (1 ). The ability of TRs to regulate transcription has been linked to their ability to recruit distinct types of transcriptional coregulatory factors, termed coactivators and corepressors, to target gene promoters (2 ,3 ). Remarkably, yeast 2-hybrid and conventional expression library screens have identified numerous TR-binding coregulatory factors (reviewed in refs. 2 and 3 ). The best characterized TR coactivators include members the p160/SRC family (2 -4 ). While the precise mechanism of action of the p160/ SRC proteins is still being defined, their ability to associate with histone acetyltransferases (HATs) such as the CREB-binding protein (CBP) and p300, and the presence of intrinsic HAT activity in some family members indicates a functional role in chromatin modification (2 -4 ).