title: Androgen receptor regulation by histone methyltransferase Suppressor of variegation 3-9 homolog 2 and Melanoma antigen-A11.
abstract: 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.
authors.affiliation: 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.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Askew
authors.affiliation: 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.
authors.forename: Suxia
authors.initials: S
authors.lastname: Bai
authors.affiliation: 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.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Parris
authors.affiliation: 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.
authors.forename: John T
authors.initials: JT
authors.lastname: Minges
authors.affiliation: 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. Electronic address: emw@med.unc.edu.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C410798:AR protein, human; D000951:Antigens, Neoplasm; C110882:MAGEA11 protein, human; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D011495:Histone-Lysine N-Methyltransferase; C515701:SUV39H2 protein, human
keywords: Androgen receptor; Histone methyltransferase; MAGE-A11; Melanoma antigen-A11; SUV39H2