Helix-loop-helix transcription factors in electrically active and inactive skeletal muscles

The muscle-specific helix-loop-helix (HLH) transcription factors myoD, myogenin, MRF4, and myf-5 are called the muscle regulatory factor family (MRF). Levels of MRFs are strongly regulated by muscle electrical activity and are thought to control downstream genes that are important for muscle phenotype such as the acetylcholine receptor (AChR) and possibly genes connected to muscle metabolic properties. The MRFs interact with ubiquitously expressed HLH factors such as E-proteins and Id-proteins to form heterodimers. In the present paper, we report the effects of paralysis obtained by nerve impulse block with tetrodotoxin (TTX) and denervation on messenger ribonucleic acid (mRNA) levels for Id-1, E47, myogenin, AChR alpha-subunit and beta-actin. Both Id-1 and E47 showed twofold increases in absence of nerve evoked electrical activity. These changes in the ubiquitously expressed HLH factors might have important functional implications for downstream gene expression, but in comparison, myogenin mRNA was increased 10-fold. We conclude that myogenin and the other muscle-specific MRFs remain the transcription factors with the strongest activity dependence that has so far been described in muscle.