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Fundamentals of DNA methylation in development

Pediatric Research volume 98, pages 458–469 (2025)Cite this article

Abstract

DNA methyation is critical to regulation of gene expression especially during developmentally dynamic changes. A large proportion occurs at CpG (a cytosine followed by a guanine nucleotide) sites and impacts gene expression based on location, timing and level of DNA methylation. The spectrum of effects produced by DNA methylation ranges from inhibition to enhancement of gene expression. Here basic terms and concepts in the study of DNA methylation are introduced. In addition, some of the commonly used techniques to assay DNA methylation are explained. New methods that allow the precise addition and removal of DNA methylation at specific sites will likely enhance our understanding of DNA methylation in development and may even lead to long-lasting therapeutic strategies to cure diseases.

Impact

  • Fundamentals of DNA methylation including its significance are made accessible to a broad audience.

  • Common assays for detecting DNA methylation are explained succinctly.

  • Developmental patterns of DNA methylation detected in commonly used animal models are discussed and explained.

  • Novel methodologies to investigate consequences of DNA methylation and demethylation are introduced.

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Fig. 1: CpG methylation.
Fig. 2: Basic genome components.
Fig. 3: Typical distribution of methylated DNA in mammalian DNA.
Fig. 4: DNA methylation controls transcription.
Fig. 5: How does methylation of DNA inhibit transcription? Answers can be gleaned from computational and experimental studies.
Fig. 6: Assays for DNA methylation.
Fig. 7: DNA methylation during development.
Fig. 8: Modified CRISPR technology to methylate and demethylate selected DNA segments.

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Acknowledgements

CAG was supported by Northern Ohio Alliance for Graduate Education and the Professoriate (NOA-AGEP) Summer Undergraduate Research Program (2018-2020), KAQ was supported by the Pediatrics Undergraduate Summer Internship Program (2020); The authors are grateful to Dr. Timothy Mead for his invaluable suggestions to the manuscript. Funding Our group is supported by R01 HL167159 (AMR), K08AA028845 (SMF) and R01HL126747 (MWJ).

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Author notes

  1. These authors contributed equally: Caitlyn A. Gillespie, Amrin Chowdhury, Katie A. Quinn.

Authors and Affiliations

  1. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA

    Caitlyn A. Gillespie, Amrin Chowdhury, Katie A. Quinn, Michael W. Jenkins, Michiko Watanabe & Stephanie M. Ford

  2. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA

    Michael W. Jenkins & Andrew M. Rollins

  3. Divisions of Neonatology and Pediatric Cardiology, UH Rainbow Babies and Children’s Hospital, Cleveland, OH, 44106, USA

    Stephanie M. Ford

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Contributions

Caitlyn A. Gillespie, Amrin Chowdhury, and Katie A. Quinn contributed equally in searching for relevant papers and reading, extracting information, and writing and rewriting substantial segments of the paper. Michael W. Jenkins and Andrew M Rollins contributed by editing text and figures and making recommendations for overall organization. Michiko Watanabe initiated the review with SMF, coordinated the efforts of CAG, AC, KAQ, and pulled together the iterations of this manuscript. Stephanie M. Ford oversaw the entire process from beginning to end, from the initiation of the review to the collection of papers to the latest version of the paper submitted.

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Correspondence to Stephanie M. Ford.

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Gillespie, C.A., Chowdhury, A., Quinn, K.A. et al. Fundamentals of DNA methylation in development. Pediatr Res 98, 458–469 (2025). https://doi.org/10.1038/s41390-024-03674-7

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