A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip

Hitoshi Hiura, Atsushi Sugawara, Hidehiko Ogawa, Rosalind M. John, Naoko Miyauchi, Yusuke Miyanari, Tokumasa Horiike, Yufeng Li, Nobuo Yaegashi, Hiroyuki Sasaki, Tomohiro Kono, Takahiro Arima

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    40 Citations (Scopus)

    Abstract

    The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpGdinucleotides 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-proteincoupled 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.

    Original languageEnglish
    Pages (from-to)4929-4945
    Number of pages17
    JournalNucleic acids research
    Volume38
    Issue number15
    DOIs
    Publication statusPublished - Apr 29 2010

    All Science Journal Classification (ASJC) codes

    • Genetics

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    Hiura, H., Sugawara, A., Ogawa, H., John, R. M., Miyauchi, N., Miyanari, Y., Horiike, T., Li, Y., Yaegashi, N., Sasaki, H., Kono, T., & Arima, T. (2010). A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. Nucleic acids research, 38(15), 4929-4945. https://doi.org/10.1093/nar/gkq200