Non-coding RNA directed DNA demethylation of Sphk1 CpG island

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

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134 Citations (Scopus)


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
Issue number2
Publication statusPublished - Sept 17 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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