URI Regulation of Androgen Receptor-Mediated Cell Growth
Annual summary rept. 4 Jun 2010-3 Jun 2013
NEW YORK UNIV NY SCHOOL OF MEDICINE
Pagination or Media Count:
Androgen receptor AR-mediated transcription is modulated by interaction with co-regulatory proteins. We identified a novel AR repressor complex comprising of the androgen receptor co-repressor Art-27 and the transcriptional repressor URI. We found through chromatin immunoprecipitation experiments that URI depletion results in increased H3K9me3 at the promoter of the AR target gene Nkx3.1, suggesting that one mechanism of URI-mediated transcriptional repression is through chromatin modification. Art-27 was also found by ChiP to localize at the transcription start site of Nkx3.1 along with PolII. Previous results demonstrated a direct interaction between URI and the transcription factor KAP1. Because of the tight association of Art-27 with URI, we hypothesized that Art-27 also affects KAP1 activity. Immunoprecipitation of Art-27 with KAP1 revealed a direct interaction between the two proteins. Consistent with this result, knockdown of Art-27 resulted in increased expression of the KAP1 targets LINE1 and AluYa5. Overall, our findings demonstrate a new role for Art-27 in KAP1-mediated gene repression.
- Anatomy and Physiology
- Medicine and Medical Research