DNA methylation in mammalian development and disease

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding of how this modification contributes to development, ageing and disease. In particular, the past decade has seen many exciting mechanistic discoveries that have...

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Bibliographic Details
Published in:Nature reviews. Genetics 2025-01, Vol.26 (1), p.7-30
Main Authors: Smith, Zachary D., Hetzel, Sara, Meissner, Alexander
Format: Article
Language:English
Subjects:
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Aging - genetics
Agriculture
Animal Genetics and Genomics
Animals
Biomedical and Life Sciences
Biomedicine
Cancer Research
DNA Methylation
DNA sequencing
Epigenesis, Genetic
Epigenetics
Gene Function
Genomics
Histones
Human Genetics
Humans
Life span
Mammals - genetics
Neoplasms - genetics
Neoplasms - metabolism
Phenotypes
Review Article
Senescence
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Summary:The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding of how this modification contributes to development, ageing and disease. In particular, the past decade has seen many exciting mechanistic discoveries that have substantially expanded our appreciation for how this generic, evolutionarily ancient modification can be incorporated into robust epigenetic codes. Here, we summarize the current understanding of the distinct DNA methylation landscapes that emerge over the mammalian lifespan and discuss how they interact with other regulatory layers to support diverse genomic functions. We then review the rising interest in alternative patterns found during senescence and the somatic transition to cancer. Alongside advancements in single-cell and long-read sequencing technologies, the collective insights made across these fields offer new opportunities to connect the biochemical and genetic features of DNA methylation to cell physiology, developmental potential and phenotype. In this Review, Smith et al. describe DNA methylation landscapes that emerge over mammalian development and within key disease states, as well as how different methyltransferases interface with histone modifications and other proteins to create and maintain them.
ISSN:1471-0056
1471-0064
1471-0064
DOI:10.1038/s41576-024-00760-8