CHAMP, a novel cardiac-specific helicase regulated by MEF2C.
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.
Liu
Z P
ZP
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
Nakagawa
O
O
Nakagawa
M
M
Yanagisawa
H
H
Passier
R
R
Richardson
J A
JA
Srivastava
D
D
Olson
E N
EN
D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D002451:Cell Compartmentation; D003001:Cloning, Molecular / Q000379:methods; D004265:DNA Helicases / Q000235:genetics*; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D064326:MEF2 Transcription Factors; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D009928:Organ Specificity; D020365:RNA Helicases; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; C477006:Mov10l1 protein, mouse; D004265:DNA Helicases; D020365:RNA Helicases