title: Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha.
abstract: In an attempt to isolate cofactors capable of influencing estrogen receptor alpha (ERalpha) transcriptional activity, we used yeast two-hybrid screening and identified protein arginine methyltransferase 2 (PRMT2) as a new ERalpha-binding protein. PRMT2 interacted directly with three ERalpha regions including AF-1, DNA binding domain, and hormone binding domain in a ligand-independent fashion. The ERalpha-interacting region on PRMT2 has been mapped to a region encompassing amino acids 133-275. PRMT2 also binds to ERbeta, PR, TRbeta, RARalpha, PPARgamma, and RXRalpha in a ligand-independent manner. PRMT2 enhanced both ERalpha AF-1 and AF-2 transcriptional activity, and the potential methyltransferase activity of PRMT2 appeared pivotal for its coactivator function. In addition, PRMT2 enhanced PR, PPARgamma, and RARalpha-mediated transactivation. Although PRMT2 was found to interact with two other coactivators, the steroid receptor coactivator-1 (SRC-1) and the peroxisome proliferator-activated receptor-interacting protein (PRIP), no synergistic enhancement of ERalpha transcriptional activity was observed when PRMT2 was coexpressed with either PRIP or SRC-1. In this respect PRMT2 differs from coactivators PRMT1 and CARM1 (coactivator-associated arginine methyltransferase). These results suggest that PRMT2 is a novel ERalpha coactivator.
authors.affiliation: Department of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chang
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Anjana V
authors.initials: AV
authors.lastname: Yeldandi
authors.forename: Sambasiva M
authors.initials: SM
authors.lastname: Rao
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D047628:Estrogen Receptor alpha; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; C000607071:RARA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D004247:DNA; D011484:Protein-Arginine N-Methyltransferases; C464934:protein arginine methyltransferase 2; D005982:Glutathione Transferase; D001616:beta-Galactosidase