Muscle type-specific RNA polymerase II recruitment during PGC-1α gene transcription after acute exercise in adult rats

Abstract

Epigenetic regulation of gene expression differs between fast- and slow-twitch skeletal muscles in adult rats, although the precise mechanisms are still unknown. The present study investigates the differences in responses of RNA polymerase II (Pol II) and histone acetylation during transcriptional activation in the plantaris and soleus muscles of adult rats after acute treadmill running. We targeted the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) gene to analyze epigenomic changes by chromatin immunoprecipitation. The mRNA expression of the PGC-1α-b isoform was significantly upregulated in both plantaris and soleus muscles 2 h after acute running, although the magnitude of the upregulation was more pronounced in the plantaris muscle. The sequences of proximal exons of the PGC-1α locus were expressed more in the plantaris muscle after acute running. Accumulation of Pol II was noted near the alternative exon 1 in both plantaris and soleus muscles in association with the enhanced distribution of acetylated histone 3. Accumulation of Pol II was also observed at the transcription start site, exon 2, and exon 3 in the plantaris muscle, but not the soleus muscle. It was noted that in the soleus muscle, acetylation of histone 3 at lysine 27 was enhanced throughout the PGC-1α locus in response to transcriptional activation, suggesting that elongating Pol II was capable of traveling through to the end of the locus. These results indicate that the mobility of Pol II during PGC-1α transcription differed between fast- and slow-twitch skeletal muscles, affecting the strength of the transcriptional activity. NEW & NOTEWORTHY Fast- and slow-twitch skeletal muscles have distinct characteristics in both force production and metabolism. Epigenetic regulations also largely differ in these muscles. Here we show that RNA polymerase II is distributed extensively at the proximal regions downstream of transcription start site during the transcriptional activation of PGC-1α in fast-twitch muscles, but it accumulates at the first exon in slow-twitch muscles. These findings will provide a basis to understand type-specific mechanisms in skeletal muscle.