論文

査読有り
2012年12月

Induction of DNA Demethylation Depending on Two Sets of Sox2 and Adjacent Oct3/4 Binding Sites (Sox-Oct Motifs) within the Mouse H19/Insulin-like Growth Factor 2 (Igf2) Imprinted Control Region

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Naohiro Hori
  • ,
  • Mariko Yamane
  • ,
  • Kaori Kouno
  • ,
  • Kenzo Sato

287
52
開始ページ
44006
終了ページ
44016
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M112.424580
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

DNA demethylation is used to establish and maintain an unmethylated state. The molecular mechanisms to induce DNA demethylation at a particular genomic locus remain unclear. The mouse H19/insulin-like growth factor 2 (Igf2) imprinted control region (ICR) is a methylation state-sensitive insulator that regulates transcriptional activation of both genes. The unmethylated state of the ICR established in female germ cells is maintained during development, resisting the wave of genome-wide de novo methylation. We previously demonstrated that a DNA fragment (fragment b) derived from this ICR-induced DNA demethylation when it was transfected into undifferentiated mouse embryonal carcinoma cell lines. Moreover, two octamer motifs within fragment b were necessary to induce this DNA demethylation. Here, we demonstrated that both octamer motifs and their flanking sequences constitute Sox-Oct motifs (SO1 and SO2) and that the SO1 region, which requires at least four additional elements, including the SO2 region, contributes significantly to the induction of high-frequency DNA demethylation as a Sox-Oct motif. Moreover, RNAi-mediated inhibition of Oct3/4 expression in P19 cells resulted in a reduced DNA demethylation frequency of fragment b but not of the adenine phosphoribosyltransferase gene CpG island. The Sox motif of SO1 could function as a sensor for a hypermethylated state of the ICR to repress demethylation activity. These results indicate that Sox-Oct motifs in the ICR determine the cell type, DNA region, and allele specificity of DNA demethylation. We propose a link between the mechanisms for maintenance of the unmethylated state of the H19/Igf2 ICR and the undifferentiated cell-specific induction of DNA demethylation.

Web of Science ® 被引用回数 : 26

リンク情報
DOI
https://doi.org/10.1074/jbc.M112.424580
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23115243
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000312940800075&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M112.424580
  • ISSN : 0021-9258
  • PubMed ID : 23115243
  • Web of Science ID : WOS:000312940800075

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