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Difference in potential DNA methylation impact on gene expression between fast- and slow-type myofibers. | LitMetric

Difference in potential DNA methylation impact on gene expression between fast- and slow-type myofibers.

Physiol Genomics

Muscle Biology Research Unit, Division of Animal Products Research, NARO Institute of Livestock and Grassland Science, Tsukuba, Japan.

Published: February 2021

AI Article Synopsis

Article Abstract

Skeletal muscles are comprised of two major types of myofibers, fast and slow. It is hypothesized that once myofiber type is determined, muscle fiber-type specificity is maintained by an epigenetic mechanism, however, this remains poorly understood. To address this, we conducted a comprehensive CpG methylation analysis with a reduced representation of bisulfite sequencing (RRBS). Using GFP- mouse, we visually distinguished and separately pooled slow-type and -negative fast-type fibers for analyses. A total of 31,967 and 26,274 CpGs were hypermethylated by ≥10% difference in the fast- and slow-type fibers, respectively. Notably, the number of promoter-hypermethylated genes with downregulated expression in the slow-type fibers was 3.5 times higher than that in the fast-type fibers. Gene bodies of the fast-type-specific myofibrillar genes , , , , and were hypermethylated in the slow-type fibers, whereas those of the slow-type-specific genes , , and were hypermethylated in the fast-type fibers. Each of the instances of gene hypermethylation was associated with the respective downregulated expression. In particular, a relationship between CpG methylation sites and the transcription variant distribution of was observed, suggesting a regulation of alternative promoter usage by gene body CpG methylation. An association of hypermethylation with the regulation of gene expression was also observed in the transcription factors and . These results suggest not only a myofiber type-specific regulation of gene expression and alternative promoter usage by gene body CpG methylation but also a dominant effect of promoter-hypermethylation on the gene expressions in slow myofibers.

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Source
http://dx.doi.org/10.1152/physiolgenomics.00099.2020DOI Listing

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