Developmental and muscle-specific changes in methylation of the myosin light chain LC1f and LC3f promoters during avian myogenesis

Abstract

The fast alkali myosin light chains LC1f and LC3f are two contractile protein isoforms encoded for by a single gene complex. Expression of these two isoforms is dependent upon differential initiation of transcription at either of two promoters encoding unique 5′ exons for isoform-specific amino termini of these light chains. Studies of protein expression have shown that the two isoforms are first expressed at different stages of development and in the case of the LC3f isoform only in fast twitch muscle fiber types. The molecular mechanisms that regulate the differential transcription of the gene complex are unknown. Experiments reported here demonstrated the direct correlation of isoform protein and mRNA expression with the undermethylation of the DNA in the promoter regions of the gene for each of the expressed myosin light chain isoforms. We find that fast and slow muscles have different patterns of undermethylation of the two promoter regions of the gene. Moreover, changes in methylation of the promoter regions were shown to occur specifically in skeletal muscle tissue, to be developmentally regulated, and to only occur in the LC3f promoter of those muscle groups that express LC3f protein.