Non-coding RNA directed DNA demethylation of Sphk1 CpG island.
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 (600-20,000nt). 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.
Imamura
Takuya
T
Laboratory of Cellular Biochemistry, Veterinary Medical Science/Animal Resource Science, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Yamamoto
Soshi
S
Ohgane
Jun
J
Hattori
Naka
N
Tanaka
Satoshi
S
Shiota
Kunio
K
D000818:Animals; D001483:Base Sequence; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D017930:Genes, Reporter; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D016372:RNA, Antisense / Q000378:metabolism*; D051381:Rats; D000099157:Sphingosine Kinase
D017853:Phosphotransferases (Alcohol Group Acceptor); D016372:RNA, Antisense; D000099157:Sphingosine Kinase