title: jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression.
abstract: Spatiotemporal regulation of cell proliferation is necessary for normal tissue development. The molecular mechanisms, especially the signaling pathways controlling the cell cycle machinery, remain largely unknown. Here, we demonstrate a negative relationship between the spatiotemporal patterns of jumonji (jmj) expression and cardiac myocyte proliferation. cyclin D1 expression and cell proliferation are enhanced in the cardiac myocytes of jmj-deficient mutant embryos. In contrast, jmj overexpression represses cyclin D1 expression in cardiac cells, and Jmj protein binds to cyclin D1 promoter in vivo and represses its transcriptional activity. cyclin D1 overexpression causes hyperproliferation in the cardiac myocytes, but the absence of cyclin D1 in jmj mutant embryos rescues the hyperproliferation. Therefore, Jmj might control cardiac myocyte proliferation and consequently cardiac morphogenesis by repressing cyclin D1 expression.
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, 194-8511, Tokyo, .
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.forename: Haruki
authors.initials: H
authors.lastname: Shirato
authors.forename: Kuniko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Mizuyo
authors.initials: M
authors.lastname: Kojima
authors.forename: Miho
authors.initials: M
authors.lastname: Takahashi
authors.forename: Misae
authors.initials: M
authors.lastname: Kubota
authors.forename: Rika
authors.initials: R
authors.lastname: Suzuki-Migishima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Motegi
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D003433:Crosses, Genetic; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D009206:Myocardium / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: C093650:Jarid2 protein, mouse; D009419:Nerve Tissue Proteins; D019938:Cyclin D1; D063151:Polycomb Repressive Complex 2