A dyad Oct-binding sequence functions as a maintenance sequence for the unmethylated state within the H19/Igf2-imprinted control region

Naohiro Hori, Hiroshi Nakano, Toshiyuki Takeuchi, Hiroyuki Kato, Sayuri Hamaguchi, Mitsuo Oshimura, Kenzo Sato

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

DNA methylation of an imprinted control region (ICR) directs the allele-specific and reciprocal expression of the mouse H19 and the insulin-like growth factor 2 (Igf2) genes, mediated by controlling enhancer access. The ICR shows enhancer blocking activity through CTCF binding to an unmethylated sequence. The unmethylated state of the maternal ICR is maintained throughout development after establishment in the germ line; however, little is known of the molecular mechanisms that regulate DNA methylation. Hence, in this study we show that a dyad Oct-binding sequence (DOS) in the ICR mediates the demethylation of low-density methylation but not hypermethylation and is required to maintain the unmethylated state against the tendency for de novo methylation within the ICR in the embryonic carcinoma cell line P19. Furthermore, we also reveal that the unmethylated state of at least one CTCF-binding site within the ICR is under the control of DOS. Our results suggest that the ICR, as a CTCF-dependent insulator, requires DOS as well as CTCF-binding sites and that DOS maintains the maternal specific unmethylated state of the ICR at postimplantation stages.

Original languageEnglish
Pages (from-to)27960-27967
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number31
DOIs
Publication statusPublished - 02-08-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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