Emily B. Askew, Suxia Bai, Amanda B. Parris, John T. Minges, Elizabeth M. Wilson. Androgen receptor regulation by histone Methyltransferase suppressor of variegation 3-9 homolog 2 andMelanomaantigen-A11. Molecular and Cellular Endocrinology 2016.
Laboratories for Reproductive Biology, Department of Pediatrics, Lineberger Comprehensive Cancer Center, and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, United States
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.
Yale Genome Editing Center, Yale School of Medicine, New Haven, CT 06510, United States.
Human Nutrition Research Program, North Carolina Central University, Kannapolis, North Carolina 28081, United States.
Marsico Lung Institute, Cystic Fibrosis Center, University of North Carolina, Chapel Hill, NC 27599, United States.
Androgen receptor (AR) transcriptional activity depends on interactions between the AR NH2-terminal region and transcriptional coregulators. A yeast two-hybrid screen of a human testis library using predicted α-helical NH2-terminal fragment AR-(370-420) as bait identified suppressor of variegation 3-9 homolog 2 (SUV39H2) histone methyltransferase as an AR interacting protein. SUV39H2 interaction with AR and the AR coregulator, melanoma antigen-A11 (MAGE-A11), was verified in two-hybrid, in vitro glutathione S-transferase affinity matrix and coimmunoprecipitation assays. Fluorescent immunocytochemistry colocalized SUV39H2 and AR in the cytoplasm without androgen, in the nucleus with androgen, and with MAGE-A11 in the nucleus independent of androgen. Chromatin immunoprecipitation using antibodies raised against SUV39H2 demonstrated androgen-dependent recruitment of AR and SUV39H2 to the androgen-responsive upstream enhancer of the prostate-specific antigen gene. SUV39H2 functioned cooperatively with MAGE-A11 to increase androgen-dependent AR transcriptional activity. SUV39H2 histone methyltransferase is an AR coactivator that increases androgen-dependent transcriptional activity through interactions with AR and MAGE-A11.