TY - JOUR
T1 - CHAMP, a novel cardiac-specific helicase regulated by MEF2C
AU - Liu, Zhi Ping
AU - Nakagawa, Osamu
AU - Nakagawa, Masayo
AU - Yanagisawa, Hiromi
AU - Passier, Robert
AU - Richardson, James A.
AU - Srivastava, Deepak
AU - Olson, Eric N.
N1 - Funding Information:
We thank A. Tizenor for assistance with graphics. O.N. was supported by the Division of Cardiovascular Medicine, Kumamoto University School of Medicine, Japan Heart Foundation & Bayer Yakuhin Research Grant Abroad, Uehara Memorial Foundation, and Yamanouchi Foundation for Research on Metabolic Disorders. R.P. was supported by the Royal Netherlands Academy of Arts and Science. D.S. was supported by grants from the National Institutes of Health (NIH) and March of Dimes. E.N.O. was supported by the NIH. This work was also supported by the D.W. Reynolds Cardiovascular Clinical Research Center.
PY - 2001/6/15
Y1 - 2001/6/15
N2 - MEF2C is a MADS-box transcription factor required for cardiac myogenesis and morphogenesis. In MEF2C mutant mouse embryos, heart development arrests at the looping stage (embryonic day 9.0), the future right ventricular chamber fails to form, and cardiomyocyte differentiation is disrupted. To identify genes regulated by MEF2C in the developing heart, we performed differential array analysis coupled with subtractive cloning using RNA from heart tubes of wild-type and MEF2C-null embryos. Here, we describe a novel MEF2C-dependent gene that encodes a cardiac-restricted protein, called CHAMP (cardiac helicase activated by MEF2 protein), that contains seven conserved motifs characteristic of helicases involved in RNA processing, DNA replication, and transcription. During mouse embryogenesis, CHAMP expression commences in the linear heart tube at embryonic day 8.0, shortly after initiation of MEF2C expression in the cardiogenic region. Thereafter, CHAMP is expressed specifically in embryonic and postnatal cardiomyocytes. At the trabeculation stage of heart development, CHAMP expression is highest in the trabecular region in which cardiomyocytes have exited the cell cycle and is lowest in the proliferative compact zone. These findings suggest that CHAMP acts downstream of MEF2C in a cardiac-specific regulatory pathway for RNA processing and/or transcriptional control.
AB - MEF2C is a MADS-box transcription factor required for cardiac myogenesis and morphogenesis. In MEF2C mutant mouse embryos, heart development arrests at the looping stage (embryonic day 9.0), the future right ventricular chamber fails to form, and cardiomyocyte differentiation is disrupted. To identify genes regulated by MEF2C in the developing heart, we performed differential array analysis coupled with subtractive cloning using RNA from heart tubes of wild-type and MEF2C-null embryos. Here, we describe a novel MEF2C-dependent gene that encodes a cardiac-restricted protein, called CHAMP (cardiac helicase activated by MEF2 protein), that contains seven conserved motifs characteristic of helicases involved in RNA processing, DNA replication, and transcription. During mouse embryogenesis, CHAMP expression commences in the linear heart tube at embryonic day 8.0, shortly after initiation of MEF2C expression in the cardiogenic region. Thereafter, CHAMP is expressed specifically in embryonic and postnatal cardiomyocytes. At the trabeculation stage of heart development, CHAMP expression is highest in the trabecular region in which cardiomyocytes have exited the cell cycle and is lowest in the proliferative compact zone. These findings suggest that CHAMP acts downstream of MEF2C in a cardiac-specific regulatory pathway for RNA processing and/or transcriptional control.
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U2 - 10.1006/dbio.2001.0277
DO - 10.1006/dbio.2001.0277
M3 - Article
C2 - 11397016
AN - SCOPUS:0035876059
SN - 0012-1606
VL - 234
SP - 497
EP - 509
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -