TY - JOUR
T1 - Non-coding RNA directed DNA demethylation of Sphk1 CpG island
AU - Imamura, Takuya
AU - Yamamoto, Soshi
AU - Ohgane, Jun
AU - Hattori, Naka
AU - Tanaka, Satoshi
AU - Shiota, Kunio
N1 - Funding Information:
We thank Y. Jouvenot and A. Paldi for support. This work was supported in part by a grant from the Program for Promotion of Basic Research Activities for Innovative Biosciences (K.S.), and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (T.I.).
PY - 2004/9/17
Y1 - 2004/9/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2004.07.159
DO - 10.1016/j.bbrc.2004.07.159
M3 - Article
C2 - 15325271
AN - SCOPUS:6044266260
SN - 0006-291X
VL - 322
SP - 593
EP - 600
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -