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Postnatal DNA demethylation and its role in tissue maturation

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Listed:
  • Yitzhak Reizel

    (Hebrew University Medical School
    Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center)

  • Ofra Sabag

    (Hebrew University Medical School)

  • Yael Skversky

    (Hebrew University Medical School)

  • Adam Spiro

    (Hebrew University Medical School)

  • Benjamin Steinberg

    (Hebrew University Medical School)

  • Diana Bernstein

    (Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center)

  • Amber Wang

    (Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center)

  • Julia Kieckhaefer

    (Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center)

  • Catherine Li

    (The Broad Institute of Harvard and MIT)

  • Eli Pikarsky

    (Hebrew University Medical School)

  • Rena Levin-Klein

    (University of Minnesota)

  • Alon Goren

    (The Broad Institute of Harvard and MIT
    University of California San Diego)

  • Klaus Rajewsky

    (Molekulare Medizin (MDC))

  • Klaus H. Kaestner

    (Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center)

  • Howard Cedar

    (Hebrew University Medical School)

Abstract

Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using a conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl-cytosine regulation as an epigenetic mechanism underlying cellular responses to a changing environment.

Suggested Citation

  • Yitzhak Reizel & Ofra Sabag & Yael Skversky & Adam Spiro & Benjamin Steinberg & Diana Bernstein & Amber Wang & Julia Kieckhaefer & Catherine Li & Eli Pikarsky & Rena Levin-Klein & Alon Goren & Klaus R, 2018. "Postnatal DNA demethylation and its role in tissue maturation," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04456-6
    DOI: 10.1038/s41467-018-04456-6
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