Main content area

α-Actinin 4 and BAT1 interaction with the Cytochrome c promoter upon skeletal muscle differentiation

Goffart, Steffi, Franko, Andras, Clemen, Christoph S., Wiesner, Rudolf J.
Current genetics 2006 v.49 no.2 pp. 125-135
DEAD-box RNA helicases, binding proteins, cell culture, cell differentiation, cytochrome c, databases, genes, heat shock proteins, muscle development, muscles, myoblasts, myotubes, rats, regulatory sequences, skeletal muscle, structural proteins
To identify common regulatory features of nuclear genes encoding mitochondrial proteins we searched for regulatory elements in the Cytochrome c promoter during skeletal muscle differentiation in cell culture. A consensus element with the sequence GCTGCCGCAC-(N4-20)-GGSCGYGGG was found in both rat Cyt c and coxIV promoters. This new sequence element with yet undescribed function, but high abundance in promoters of nuclear genes encoding mitochondrial proteins available from the databases, showed a striking change in protein binding in electromobility shift assays when myoblasts were compared to myotubes. Proteins involved in the observed protein-DNA complexes were isolated from myotubes and identified by MALDI-TOF as BAT1, a DEAD-box protein of yet unknown function, heat shock protein HSP84, and α-actinin 4, a non-muscle isoform of the structural protein α-actinin. α-actinin 4 was found to be preferentially localized in the nucleus upon induction of myogenesis, suggesting a signaling function during muscle differentiation. In conclusion, the analyzed sequence motif may be a new candidate for common regulatory elements specific for nuclear encoded mitochondrial genes, and α-actinin 4 may be involved in their regulation.