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Chen DY, Ferguson IM, Braun KA, et al. Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype. Proc Natl Acad Sci U S A. 2021;118(16)doi: 10.1073/pnas.2022760118.
Chen, D. Y., Ferguson, I. M., Braun, K. A., Sutton, L. A., Helton, N. M., Ramakrishnan, S. M., Smith, A. M., Miller, C. A., & Ley, T. J. (2021). Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype. Proceedings of the National Academy of Sciences of the United States of America, 118(16), . https://doi.org/10.1073/pnas.2022760118
Chen, David Y, et al. "Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype." Proceedings of the National Academy of Sciences of the United States of America vol. 118,16 (2021). doi: https://doi.org/10.1073/pnas.2022760118
Chen DY, Ferguson IM, Braun KA, Sutton LA, Helton NM, Ramakrishnan SM, Smith AM, Miller CA, Ley TJ. Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype. Proc Natl Acad Sci U S A. 2021 Apr 20;118(16). doi: 10.1073/pnas.2022760118. PMID: 33846253; PMCID: PMC8072215.
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Proc Natl Acad Sci U S A. 2021 Apr 20;118(16). doi: 10.1073/pnas.2022760118.

Dnmt3a deficiency in the skin causes focal, canonical DNA hypomethylation and a cellular proliferation phenotype.

Proceedings of the National Academy of Sciences of the United States of America

David Y Chen, Ian M Ferguson, Krista A Braun, Leslie A Sutton, Nichole M Helton, Sai Mukund Ramakrishnan, Amanda M Smith, Christopher A Miller, Timothy J Ley

Affiliations

  1. Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
  2. Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
  3. Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110 [email protected].

PMID: 33846253 PMCID: PMC8072215 DOI: 10.1073/pnas.2022760118

Abstract

DNA hypomethylation is a feature of epidermal cells from aged and sun-exposed skin, but the mechanisms responsible for this methylation loss are not known. Dnmt3a is the dominant de novo DNA methyltransferase in the skin; while epidermal Dnmt3a deficiency creates a premalignant state in which keratinocytes are more easily transformed by topical mutagens, the conditions responsible for this increased susceptibility to transformation are not well understood. Using whole genome bisulfite sequencing, we identified a focal, canonical DNA hypomethylation phenotype in the epidermal cells of Dnmt3a-deficient mice. Single-cell transcriptomic analysis revealed an increased proportion of cells with a proliferative gene expression signature, while other populations in the skin were relatively unchanged. Although total DNMT3A deficiency has not been described in human disease states, rare patients with an overgrowth syndrome associated with behavioral abnormalities and an increased risk of cancer often have heterozygous, germline mutations in

Copyright © 2021 the Author(s). Published by PNAS.

Keywords: DNA methylation; DNMT3A; epidermis; epigenetic; premalignant

Conflict of interest statement

The authors declare no competing interest.

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