DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: De novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation

Kohei Miyata, Tomoko Miyata, Kazuhiko Nakabayashi, Kohji Okamura, Masashi Naito, Tomoko Kawai, Shuji Takada, Kiyoko Kato, Shingo Miyamoto, Kenichiro Hata, Hiroshi Asahara

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Although DNA methylation is considered to playanimportant role duringmyogenic differentiation, chronological alterations in DNA methylation and gene expression patterns in this process have been poorly understood. Using the Infinium Human Methylation 450 BeadChip array, we obtained a chronological profile of the genomewide DNA methylation status in a human myoblast differentiation model, where myoblasts were cultured in low-serum medium to stimulate myogenic differentiation. As the differentiation of the myoblasts proceeded, their global DNA methylation level increased and their methylation patterns became more distinct from those of mesenchymal stem cells. Gene ontology analysis revealed that genes whose promoter region was hypermethylated upon myoblast differentiation were highly significantly enriched with muscle-related terms such as 'muscle contraction' and 'muscle system process'. Sequence motif analysis identified 8-bp motifs somewhat similar to the binding motifs of ID4 and ZNF238 to be most significantly enriched in hypermethylated promoter regions. ID4 and ZNF238 have been shown to be critical transcriptional regulators of muscle-related genes during myogenic differentiation. Anintegrated analysis of DNA methylation and gene expression profiles revealed that de novo DNA methylation of non-CpG island (CGI) promoters was more often associated with transcriptional down-regulation than that of CGI promoters. These results strongly suggest the existence of an epigenetic mechanism in which DNA methylation modulates the functions of key transcriptional factors to coordinately regulate muscle-related genes during myogenic differentiation.

Original languageEnglish
Article numberddu457
Pages (from-to)410-423
Number of pages14
JournalHuman molecular genetics
Volume24
Issue number2
DOIs
Publication statusPublished - Jan 15 2015

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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