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Atlas of imprinted and allele-specific DNA methylation in the human body

Author

Listed:
  • Jonathan Rosenski

    (The Hebrew University of Jerusalem)

  • Ayelet Peretz

    (The Hebrew University of Jerusalem)

  • Judith Magenheim

    (The Hebrew University of Jerusalem)

  • Netanel Loyfer

    (The Hebrew University of Jerusalem)

  • Ruth Shemer

    (The Hebrew University of Jerusalem)

  • Benjamin Glaser

    (The Hebrew University of Jerusalem)

  • Yuval Dor

    (The Hebrew University of Jerusalem
    The Hebrew University of Jerusalem)

  • Tommy Kaplan

    (The Hebrew University of Jerusalem
    The Hebrew University of Jerusalem
    The Hebrew University of Jerusalem)

Abstract

Allele-specific DNA methylation reflects genetic variation and parentally-inherited changes, and is involved in gene regulation and pathologies. Yet, our knowledge of this phenomenon is largely limited to blood. Here we present a comprehensive atlas of allele-specific DNA methylation using deep whole-genome sequencing across 39 normal human cell types. We identified 325k regions, covering 6% of the genome and 11% of CpGs, that show a bimodal distribution of methylated and unmethylated molecules. In 34k of these regions, genetic variations at individual alleles segregate with methylation patterns, validating allele-specific methylation. We also identified 460 regions showing parental allele-specific methylation, the majority of which are novel, as well as 78 regions associated with known imprinted genes. Surprisingly, sequence-dependent and parental allele-dependent methylation is often restricted to specific cell types, revealing unappreciated variation of allele-specific methylation across the human body. Finally, we validate tissue-specific, maternal allele-specific methylation of CHD7, offering a potential mechanism for the paternal bias in the inheritance mode of CHARGE syndrome associated with this gene. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types.

Suggested Citation

  • Jonathan Rosenski & Ayelet Peretz & Judith Magenheim & Netanel Loyfer & Ruth Shemer & Benjamin Glaser & Yuval Dor & Tommy Kaplan, 2025. "Atlas of imprinted and allele-specific DNA methylation in the human body," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57433-1
    DOI: 10.1038/s41467-025-57433-1
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