jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression.
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.
Toyoda
Masashi
M
Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, 194-8511, Tokyo, .
Shirato
Haruki
H
Nakajima
Kuniko
K
Kojima
Mizuyo
M
Takahashi
Miho
M
Kubota
Misae
M
Suzuki-Migishima
Rika
R
Motegi
Yoshiko
Y
Yokoyama
Minesuke
M
Takeuchi
Takashi
T
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
C093650:Jarid2 protein, mouse; D009419:Nerve Tissue Proteins; D019938:Cyclin D1; D063151:Polycomb Repressive Complex 2