title: Negative regulation of transcription by the type II arginine methyltransferase PRMT5.
abstract: We have identified previously a repressor element in the transcription start site region of the cyclin E1 promoter that periodically associates with an atypical, high molecular weight E2F complex, termed CERC. Purification of native CERC reveals the presence of the type II arginine methyltransferase PRMT5, which can mono- or symetrically dimethylate arginine residues in proteins. Chromatin immunoprecipitations (ChIPs) show that PRMT5 is associated specifically with the transcription start site region of the cyclin E1 promoter. ChIP analyses also show that this correlates with the presence on the same promoter region of arginine-methylated proteins including histone H4, an in vitro substrate of PRMT5. Consistent with its presence within the repressor complex, forced expression of PRMT5 negatively affects cyclin E1 promoter activity and cellular proliferation, effects that require its methyltransferase activity. These data provide the first direct experimental evidence that a type II arginine methylase is involved in the control of transcription and proliferation.
authors.affiliation: Institut de Génétique Moleculaire, Montpellier cedex 5, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Fabbrizio
authors.forename: Selma
authors.initials: S
authors.lastname: El Messaoudi
authors.forename: Jolanta
authors.initials: J
authors.lastname: Polanowska
authors.forename: Conception
authors.initials: C
authors.lastname: Paul
authors.forename: Jeffry R
authors.initials: JR
authors.lastname: Cook
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Vincent
authors.initials: V
authors.lastname: Negre
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rousset
authors.forename: Sidney
authors.initials: S
authors.lastname: Pestka
authors.forename: Alphonse
authors.initials: A
authors.lastname: Le Cam
authors.forename: Claude
authors.initials: C
authors.lastname: Sardet
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001120:Arginine / Q000378:metabolism; D020134:Catalytic Domain; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014982:Xenopus laevis
chemical_list: D002843:Chromatin; D019927:Cyclin E; D046911:Macromolecular Substances; D012097:Repressor Proteins; D001120:Arginine; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases