Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development

Hiroaki Okae, Hatsune Chiba, Hitoshi Hiura, Hirotaka Hamada, Akiko Sato, Takafumi Utsunomiya, Hiroyuki Kikuchi, Hiroaki Yoshida, Atsushi Tanaka, Mikita Suyama, Takahiro Arima

    Research output: Contribution to journalArticle

    107 Citations (Scopus)

    Abstract

    DNA methylation is globally reprogrammed during mammalian preimplantation development, which is critical for normal development. Recent reduced representation bisulfite sequencing (RRBS) studies suggest that the methylome dynamics are essentially conserved between human and mouse early embryos. RRBS is known to cover 5–10% of all genomic CpGs, favoring those contained within CpG-rich regions. To obtain an unbiased and more complete representation of the methylome during early human development, we performed whole genome bisulfite sequencing of human gametes and blastocysts that covered>70% of all genomic CpGs. We found that the maternal genome was demethylated to a much lesser extent in human blastocysts than in mouse blastocysts, which could contribute to an increased number of imprinted differentially methylated regions in the human genome. Global demethylation of the paternal genome was confirmed, but SINE-VNTR-Alu elements and some other tandem repeat-containing regions were found to be specifically protected from this global demethylation. Furthermore, centromeric satellite repeats were hypermethylated in human oocytes but not in mouse oocytes, which might be explained by differential expression of de novo DNA methyltransferases. These data highlight both conserved and species-specific regulation of DNA methylation during early mammalian development. Our work provides further information critical for understanding the epigenetic processes underlying differentiation and pluripotency during early human development.

    Original languageEnglish
    JournalPLoS genetics
    Volume10
    Issue number12
    DOIs
    Publication statusPublished - Dec 1 2014

    Fingerprint

    human development
    methylation
    Human Development
    DNA methylation
    DNA Methylation
    Blastocyst
    genome
    bisulfites
    Genome
    DNA
    blastocyst
    Oocytes
    genomics
    Short Interspersed Nucleotide Elements
    Genetic Epigenesis
    Alu Elements
    mice
    oocytes
    Tandem Repeat Sequences
    Methyltransferases

    All Science Journal Classification (ASJC) codes

    • Ecology, Evolution, Behavior and Systematics
    • Molecular Biology
    • Genetics
    • Genetics(clinical)
    • Cancer Research

    Cite this

    Okae, H., Chiba, H., Hiura, H., Hamada, H., Sato, A., Utsunomiya, T., ... Arima, T. (2014). Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development. PLoS genetics, 10(12). https://doi.org/10.1371/journal.pgen.1004868

    Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development. / Okae, Hiroaki; Chiba, Hatsune; Hiura, Hitoshi; Hamada, Hirotaka; Sato, Akiko; Utsunomiya, Takafumi; Kikuchi, Hiroyuki; Yoshida, Hiroaki; Tanaka, Atsushi; Suyama, Mikita; Arima, Takahiro.

    In: PLoS genetics, Vol. 10, No. 12, 01.12.2014.

    Research output: Contribution to journalArticle

    Okae, H, Chiba, H, Hiura, H, Hamada, H, Sato, A, Utsunomiya, T, Kikuchi, H, Yoshida, H, Tanaka, A, Suyama, M & Arima, T 2014, 'Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development', PLoS genetics, vol. 10, no. 12. https://doi.org/10.1371/journal.pgen.1004868
    Okae, Hiroaki ; Chiba, Hatsune ; Hiura, Hitoshi ; Hamada, Hirotaka ; Sato, Akiko ; Utsunomiya, Takafumi ; Kikuchi, Hiroyuki ; Yoshida, Hiroaki ; Tanaka, Atsushi ; Suyama, Mikita ; Arima, Takahiro. / Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development. In: PLoS genetics. 2014 ; Vol. 10, No. 12.
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