FUNCTION OF NUCLEAR CO-REPRESSOR PROTEIN ON THYROID-HORMONE RESPONSE ELEMENTS IS REGULATED BY THE RECEPTOR A B DOMAIN/

Recently, a family of nuclear co-repressor proteins (TRACs) have been identified that interact with thyroid hormone (TR) and retinoic acid r eceptors to mediate Ligand-independent repression of gene transcriptio n. In this report, we have cloned and characterized a human TRAC, whic h when expressed as a truncated protein lacking its repressing domains , can abolish endogenous cellular TRAC activity. Use of this inhibitor has uncovered a differential function of TRACs on negative versus pos itive thyroid hormone response elements and has demonstrated the impor tance of the TR A/B domain in modulating TRAC function. Thus, isoform- specific functions of the TR may be mediated by their functional inter action with co-repressor proteins.