Sequential changes in genome-wide DNA methylation status during adipocyte differentiation

Hideki Sakamoto, Yasushi Kogo, Jun Ohgane, Naka Hattori, Shintaro Yagi, Satoshi Tanaka, Kunio Shiota*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


DNA methylation is an epigenetic mark on the mammalian genome. There are numerous tissue-dependent and differentially methylated regions (T-DMRs) in the unique sequences distributed throughout the genome. To determine the epigenetic changes during adipocyte differentiation, we investigated the sequential changes in DNA methylation status of 3T3-L1 cells at the growing, confluent, postconfluent and mature adipocyte cell stages. Treatment of 3T3-L1 cells with 5-aza-2′-deoxycytidine inhibited differentiation in a stage-dependent manner, supporting the idea that formation of accurate DNA methylation profile, consisting of methylated and unmethylated T-DMRs, may be involved in differentiation. Analysis by methylation-sensitive quantitative real-time PCR of the 65 known T-DMRs which contain NotI sites detected 8 methylations that changed during differentiation, and the changes in the patterns of these methylations were diverse, confirming that the differentiation process involves epigenetic alteration at the T-DMRs. Intriguingly, the dynamics of the methylation change vary depending on the T-DMRs and differentiation stages. Restriction landmark genomic scanning detected 32 novel T-DMRs, demonstrating that differentiation of 3T3-L1 cells involves genome-wide epigenetic changes by temporal methylation/demethylation, in addition to maintenance of a static methylated/demethylated state, and both depend on differentiation stage.

Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2008 Feb 8
Externally publishedYes


  • Adipocyte differentiation
  • DNA methylation
  • Restriction landmark genomic scanning
  • Tissue-dependent and differentially methylated regions

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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