Accumulation and loss of asymmetric non-CpG methylation during male germ-cell development

Tomoko Ichiyanagi, Kenji Ichiyanagi, Miho Miyake, Hiroyuki Sasaki

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    Abstract

    DNA methylation is a well-characterized epigenetic modification involved in gene regulation and transposon silencing in mammals. It mainly occurs on cytosines at CpG sites but methylation at non-CpG sites is frequently observed in embryonic stem cells, induced pluriotent stem cells, oocytes and the brain. The biological significance of non-CpG methylation is unknown. Here, we show that non-CpG methylation is also present in male germ cells, within and around B1 retrotransposon sequences interspersed in the mouse genome. It accumulates in mitotically arrested fetal prospermatogonia and reaches the highest level by birth in a Dnmt3l-dependent manner. The preferential site of non-CpG methylation is CpA, especially CpApG and CpApC. Although CpApG (and CpTpG) sites contain cytosines at symmetrical positions, hairpin-bisulfite sequencing reveals that they are hemimethylated, suggesting the absence of a template-dependent copying mechanism. Indeed, the level of non-CpG methylation decreases after the resumption of mitosis in the neonatal period, whereas that of CpG methylation does not. The cells eventually lose non-CpG methylation by the time they become spermatogonia. Our results show that non-CpG methylation accumulates in non-replicating, arrested cells but is not maintained in mitotically dividing cells during male germ-cell development.

    Original languageEnglish
    Pages (from-to)738-745
    Number of pages8
    JournalNucleic Acids Research
    Volume41
    Issue number2
    DOIs
    Publication statusPublished - Jan 1 2013

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    Germ Cells
    Methylation
    Cytosine
    Retroelements
    Spermatogonia
    DNA Methylation
    Embryonic Stem Cells
    Mitosis
    Epigenomics
    Oocytes
    Mammals
    Stem Cells
    Parturition
    Genome
    Brain
    Genes

    All Science Journal Classification (ASJC) codes

    • Genetics

    Cite this

    Accumulation and loss of asymmetric non-CpG methylation during male germ-cell development. / Ichiyanagi, Tomoko; Ichiyanagi, Kenji; Miyake, Miho; Sasaki, Hiroyuki.

    In: Nucleic Acids Research, Vol. 41, No. 2, 01.01.2013, p. 738-745.

    Research output: Contribution to journalArticle

    Ichiyanagi, Tomoko ; Ichiyanagi, Kenji ; Miyake, Miho ; Sasaki, Hiroyuki. / Accumulation and loss of asymmetric non-CpG methylation during male germ-cell development. In: Nucleic Acids Research. 2013 ; Vol. 41, No. 2. pp. 738-745.
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