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Curr Genet. 2006 Feb;49(2):125-35. Epub 2005 Dec 6.

Alpha-actinin 4 and BAT1 interaction with the cytochrome c promoter upon skeletal muscle differentiation.

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Institute of Vegetative Physiology, Medical Faculty, University of Köln, Germany.


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.

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