Alpha-actinin 4 and BAT1 interaction with the cytochrome c promoter upon skeletal muscle differentiation.
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 alpha-actinin 4, a non-muscle isoform of the structural protein alpha-actinin. alpha-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 alpha-actinin 4 may be involved in their regulation.
Goffart
Steffi
S
Institute of Vegetative Physiology, Medical Faculty, University of Köln, Germany. steffi.goffart@uta.fi
Franko
Andras
A
Clemen
Christoph S
CS
Wiesner
Rudolf J
RJ
D000185:Actinin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019295:Computational Biology; D045304:Cytochromes c / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009154:Mutation; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats
C491752:Actn4 protein, mouse; D000185:Actinin; D045304:Cytochromes c; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases