Epigenetics of Genes Displaying High and Preferential Expression in Myoblasts

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background/objectives Genome-wide studies of differential DNA methylation often focus on its role in turning transcription on or off. Here we report some atypical epigenetic/transcription relationships for 92 genes that are highly and preferentially expressed in primary human myoblasts relative to heterologous cell cultures. Methods We compared methylomes and myoblast-specific differentially methylated regions (DMRs) with methylomes, chromatin profiles, and transcriptomes for many different cell populations. Results We found that myoblast-associated promoter hypomethylation was unusually prevalent among the 92 myoblast-preferential genes. Sometimes this promoter hypomethylation was seen as a myoblast-associated extension of their constitutively unmethylated region at a CpG island. All 92 genes showed some myoblast-specific hypomethylation, including 32 genes at tissue-specific super-enhancers or broad H3K4-trimethylated promoters. Myoblast hypermethylated DMRs were also associated with almost half of the myoblast-preferential genes. These hypermethylated DMRs were often in intragenic locations embedded in H3K36-trimethylated chromatin in myoblasts. Conclusions Our analysis suggests that some of the hypermethylated DMRs repress cryptic, alternative, or adjacent promoters. Myoblast hypermethylated DMRs may also downmodulate expression in myoblasts to avoid yet higher RNA levels f

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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