Isoform-specific interaction of HP1 with human TAF_II130

Abstract

The general transcription factor TFIID facilitates recruitment of the transcription machinery to gene promoters and regulates initiation of transcription by RNA polymerase II. hTAF_II130, a component of TFIID, interacts with and serves as a coactivator for multiple transcriptional regulatory proteins, including Sp1 and CREB. A yeast two-hybrid screen has identified an interaction between hTAF_II130 and heterochromatin protein 1 (HP1), a chromatin-associated protein whose function has been implicated in gene silencing. We find that hTAF_II130 associates with HP1 in an isoform-specific manner: HP1α and HP1γ bind to hTAF_II130, but not HP1β. In addition, we show that endogenous hTAF_II130 and components of TFIID in HeLa nuclear extracts associate with glutathione S-transferase-HP1α and -HP1γ. hTAF_II130 possesses a pentapeptide HP1-binding motif, and mutation of the hTAF_II130 HP1 box compromises the interaction of hTAF_II130 with HP1. We demonstrate that Gal4-HP1 proteins interfere with hTAF_II130-mediated activation of transcription. Our results suggest that HP1α and HP1γ associate with hTAF_II130 to mediate repression of transcription, supporting a new model of transcriptional repression involving a specific interaction between a component of TFIID and chromatin.