Project description:DNA methylation occurs as 5-methylcytosines mainly at cytosine-guanine dinucleotides, so-called CpG sites, and such methylation is a well-studied epigenetic mechanism for transcriptional regulation. Generally, DNA methylation of the gene promoter is correlated with transcriptional repression. Genomic DNA methylation patterns are established by the actions of the de novo methyltransferases Dnmt3a and Dnmt3b, and are maintained by the methyltransferase Dnmt1. Expression of Dnmt3a mRNA is relatively high in skeletal muscle, suggesting a major role in transcriptional regulation. Also, denervation of skeletal muscle decreased expression of Dnmt3a mRNA, suggesting involvement of Dnmt3a in pathophysiology during atrophy. Decreased regeneration capacity in atrophied skeletal muscle hampers muscle mass recovery after injury and the impaired muscle function, lowers the quality of life. We found that in skeletal muscle of atrophy models, Dnmt3a was decreased. Muscle regeneration was delayed in the skeletal muscle-specific Dnmt3a knockout (Dnmt3a-KO) mice, in which Dnmt3a was deleted in skeletal muscle as well as in satellite cells, important for muscle regeneration. In this study, we used Dnmt3a-KO mice, and attempt to clarify the mechanism of reduced muscle regeneration during atrophy. The microarray data shows that expression of a Gdf/Bmp family protein Gdf5, which suppressed differentiation of satellite cells, is activated in Dnmt3a-KO mice compared with wild-type mice.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
