p62, A TFIIH subunit, directly interacts with thyroid hormone receptor and enhances T3-mediated transcription.

Currently, little is known about the direct interactions of general transcription factors and nuclear hormone receptors. To investigate the potential role of the general transcription factor, TFIIH, in T3-mediated transcriptional activation, we examined thyroid hormone receptor (TR) interaction with individual TFIIH subunits in a yeast-two hybrid system. Among the nine subunits of TFIIH studied, only p62 subunit interacted with TRbeta in a ligand-dependent manner. Glutathione-S-transferase pull-down and in vivo coimmunoprecipitation studies also demonstrated direct TR/p62 interaction. Using chromatin immunoprecipitation assays, we showed that TFIIH subunits were corecruited on or near an endogenous thyroid hormone response element upon T3 addition. Cotransfection studies with TSA201 cells showed that p62 increased T3-mediated transcription, which could be further enhanced when p62 and another TFIIH subunit, p44, were cotransfected simultaneously. Taken together, these data suggest that TRs can interact directly with a subunit of TFIIH and may provide an alternative pathway for nuclear receptor communication with the general transcription machinery that circumvents coactivators.

Duke Scholars

Author Paul Michael Yen Medicine, Endocrinology, Metabolism, and Nutrition