BIOCHEMISTRY AND GENETICS OF THYROID HORMONE RECEPTORS

Baylor College Of Medicine, Houston TX

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Abstract

DESCRIPTION: The function of thyroid hormone receptors (TRs) as ligand dependent transcription factors is mediated by their interaction with a variety of proteins. Over the previous funding period the major focus of this project was identification and characterization of TR interacting proteins (TRIPs) and more than 20 were identified. The focus of the current period is on the mechanism of action of a subset of these TR interactors in both chromatin and non-chromatin contexts. The first specific aim is to characterize in detail the biochemical basis of the strong stimulatory effect of TRIP7, a nucleosomal protein, on TR DNA binding, and to determine functional consequences of this effect. The second specific aim is to test the hypothesis that the SWI/SNF complex is involved in the chromatin remodeling associated with activation by the TRs and, more broadly, to characterize the functional role of the SWI/SNF complex in TR action. The third aim is to characterize the mechanism of action of the recently identified potential co-activator TRIP4 that does not appear to act at the chromatin level. The final aim is to continue to maintain and develop the Thyroid hormone Receptor Resource, a web-based source of information on the TRs.