Non-coding RNA directed DNA demethylation of Sphk1 CpG island

Takuya Imamura, Soshi Yamamoto, Jun Ohgane, Naka Hattori, Satoshi Tanaka, Kunio Shiota

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The formation of DNA methylation patterns is one of the epigenetic events that underlie mammalian development. The Sphk1 CpG island is a target for tissue-dependent DNA methylation as well as a template for generating multiple subtypes. The number of mammalian non-coding RNA genes is rapidly expanding. In this study, we found endogenous antisense transcripts, Khps1 subtypes with different sizes (600-20,000 nt). A subtype, Khps1a, was a 1290-bp, non-coding, 5′-capped and 3′-polyadenylated RNA that originated from the CpG island and overlapped with a tissue-dependent differentially methylated region (T-DMR) of Sphk1. Intriguingly, overexpression of two fragments of Khps1 caused demethylation of CG sites in the T-DMR. Furthermore, this RNA-directed demethylation was associated with DNA methylation at three CC(A/T)GG sites in the T-DMR. The link between the RNA-directed CG demethylation and non-CG methylation provides a novel mechanism of epigenetic regulation and potential tool for epigenetic manipulation of mammalian cells.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume322
Issue number2
DOIs
Publication statusPublished - 2004 Sep 17
Externally publishedYes

Keywords

  • Antisense RNA
  • CpG island
  • Demethylation
  • DNA methylation
  • Non-coding
  • Sphingosine kinase
  • Tissue-specific

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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  • Cite this

    Imamura, T., Yamamoto, S., Ohgane, J., Hattori, N., Tanaka, S., & Shiota, K. (2004). Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochemical and Biophysical Research Communications, 322(2), 593-600. https://doi.org/10.1016/j.bbrc.2004.07.159