title: Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.
abstract: In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).
authors.affiliation: Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Drive, Building 41, Room B302, Bethesda, MD 20892, USA.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hanxin
authors.initials: H
authors.lastname: Lu
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.forename: Hyeon Ung
authors.initials: HU
authors.lastname: Park
authors.forename: Cynthia
authors.initials: C
authors.lastname: Pise-Masison
authors.forename: John N
authors.initials: JN
authors.lastname: Brady
mesh_terms: D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism*; D016356:Gene Products, tax / Q000378:metabolism*; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D018613:Microscopy, Confocal; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic
chemical_list: D004279:DNA, Viral; D016356:Gene Products, tax; D006657:Histones; D008156:Luciferases; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1