A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip.
The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpG-dinucleotides at differentially methylated regions (DMRs) during gametogenesis. To date, four paternally methylated DMRs have been identified in screens based on conventional approaches. These DMRs are linked to the imprinted genes H19, Gtl2 (IG-DMR), Rasgrf1 and, most recently, Zdbf2 which encodes zinc finger, DBF-type containing 2. In this study, we applied a novel methylated-DNA immunoprecipitation-on-chip (meDIP-on-chip) method to genomic DNA from mouse parthenogenetic- and androgenetic-derived stem cells and sperm and identified 458 putative DMRs. This included the majority of known DMRs. We further characterized the paternally methylated Zdbf2/ZDBF2 DMR. In mice, this extensive germ line DMR spanned 16 kb and possessed an unusual tripartite structure. Methylation was dependent on DNA methyltransferase 3a (Dnmt3a), similar to H19 DMR and IG-DMR. In both humans and mice, the adjacent gene, Gpr1/GPR1, which encodes a G-protein-coupled receptor 1 protein with transmembrane domain, was also imprinted and paternally expressed. The Gpr1-Zdbf2 domain was most similar to the Rasgrf1 domain as both DNA methylation and the actively expressed allele were in cis on the paternal chromosome. This work demonstrates the effectiveness of meDIP-on-chip as a technique for identifying DMRs.
Hiura
Hitoshi
H
Innovation of New Biomedical Engineering Center, University of Tohoku, Aoba-ku, Sendai, Japan.
Sugawara
Atsushi
A
Ogawa
Hidehiko
H
John
Rosalind M
RM
Miyauchi
Naoko
N
Miyanari
Yusuke
Y
Horiike
Tokumasa
T
Li
Yufeng
Y
Yaegashi
Nobuo
N
Sasaki
Hiroyuki
H
Kono
Tomohiro
T
Arima
Takahiro
T
D000818:Animals; D047369:Chromatin Immunoprecipitation; D033481:Chromosomes, Mammalian; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D043562:Receptors, G-Protein-Coupled; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
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