CHAMP, a novel cardiac-specific helicase regulated by MEF2C

MEF2C is a MADS-box transcription factor required for cardiac myogenesis an d morphogenesis. In MEF2C mutant mouse embryos, heart development arrests a t the looping stage (embryonic day 9.0), the future right ventricular chamb er fails to form, and cardiomyocyte differentiation is disrupted. To identi fy genes regulated by MEF2C in the developing heart, we performed different ial array analysis coupled with subtractive cloning using RNA from heart tu bes of wild-type and MEF2C-null embryos. Here, we describe a novel MEF2C-de pendent gene that encodes a cardiac-restricted protein, called CHAMP (cardi ac helicase activated by MEF2 protein), that contains seven conserved motif s characteristic of helicases involved in RNA processing, DNA replication, and transcription. During mouse embryogenesis, CHAMP expression commences i n the linear heart tube at embryonic day 8.0, shortly after initiation of M EF2C expression in the cardiogenic region. Thereafter, CHAMP is expressed s pecifically 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 down stream of MEF2C in a cardiac-specific regulatory pathway for RNA processing and/or transcriptional control. (C) 2001 Academic Press.