De novo DNA methylation drives 5hmC accumulation in mouse zygotes

Rachel Amouroux, Buhe Nashun, Kenjiro Shirane, Shoma Nakagawa, Peter W.S. Hill, Zelpha D'Souza, Manabu Nakayama, Masashi Matsuda, Aleksandra Turp, Elodie Ndjetehe, Vesela Encheva, Nobuaki R. Kudo, Haruhiko Koseki, Hiroyuki Sasaki, Petra Hajkova

    Research output: Contribution to journalArticle

    87 Citations (Scopus)

    Abstract

    Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs 1-4). Here we demonstrate using detailed immunofluorescence analysis and ultrasensitive LC-MS-based quantitative measurements that the initial loss of paternal 5mC does not require 5hmC formation. Small-molecule inhibition of Tet3 activity, as well as genetic ablation, impedes 5hmC accumulation in zygotes without affecting the early loss of paternal 5mC. Instead, 5hmC accumulation is dependent on the activity of zygotic Dnmt3a and Dnmt1, documenting a role for Tet3-driven hydroxylation in targeting de novo methylation activities present in the early embryo. Our data thus provide further insights into the dynamics of zygotic reprogramming, revealing an intricate interplay between DNA demethylation, de novo methylation and Tet3-driven hydroxylation.

    Original languageEnglish
    Pages (from-to)225-233
    Number of pages9
    JournalNature Cell Biology
    Volume18
    Issue number2
    DOIs
    Publication statusPublished - Jan 28 2016

    Fingerprint

    5-Methylcytosine
    Zygote
    DNA Methylation
    Hydroxylation
    Methylation
    Dioxygenases
    DNA
    Epigenomics
    Fluorescent Antibody Technique
    Embryonic Structures
    Genome

    All Science Journal Classification (ASJC) codes

    • Cell Biology

    Cite this

    Amouroux, R., Nashun, B., Shirane, K., Nakagawa, S., Hill, P. W. S., D'Souza, Z., ... Hajkova, P. (2016). De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nature Cell Biology, 18(2), 225-233. https://doi.org/10.1038/ncb3296

    De novo DNA methylation drives 5hmC accumulation in mouse zygotes. / Amouroux, Rachel; Nashun, Buhe; Shirane, Kenjiro; Nakagawa, Shoma; Hill, Peter W.S.; D'Souza, Zelpha; Nakayama, Manabu; Matsuda, Masashi; Turp, Aleksandra; Ndjetehe, Elodie; Encheva, Vesela; Kudo, Nobuaki R.; Koseki, Haruhiko; Sasaki, Hiroyuki; Hajkova, Petra.

    In: Nature Cell Biology, Vol. 18, No. 2, 28.01.2016, p. 225-233.

    Research output: Contribution to journalArticle

    Amouroux, R, Nashun, B, Shirane, K, Nakagawa, S, Hill, PWS, D'Souza, Z, Nakayama, M, Matsuda, M, Turp, A, Ndjetehe, E, Encheva, V, Kudo, NR, Koseki, H, Sasaki, H & Hajkova, P 2016, 'De novo DNA methylation drives 5hmC accumulation in mouse zygotes', Nature Cell Biology, vol. 18, no. 2, pp. 225-233. https://doi.org/10.1038/ncb3296
    Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill PWS, D'Souza Z et al. De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nature Cell Biology. 2016 Jan 28;18(2):225-233. https://doi.org/10.1038/ncb3296
    Amouroux, Rachel ; Nashun, Buhe ; Shirane, Kenjiro ; Nakagawa, Shoma ; Hill, Peter W.S. ; D'Souza, Zelpha ; Nakayama, Manabu ; Matsuda, Masashi ; Turp, Aleksandra ; Ndjetehe, Elodie ; Encheva, Vesela ; Kudo, Nobuaki R. ; Koseki, Haruhiko ; Sasaki, Hiroyuki ; Hajkova, Petra. / De novo DNA methylation drives 5hmC accumulation in mouse zygotes. In: Nature Cell Biology. 2016 ; Vol. 18, No. 2. pp. 225-233.
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