Smith Zachary D, Hetzel Sara, Meissner Alexander
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nat Rev Genet. 2025 Jan;26(1):7-30. doi: 10.1038/s41576-024-00760-8. Epub 2024 Aug 12.
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.
DNA甲基化领域已从发现和基因组特征描述阶段发展到一个寻求更深入功能理解的阶段，即这种修饰如何对发育、衰老和疾病产生影响。特别是在过去十年中，出现了许多令人兴奋的机制发现，这些发现极大地扩展了我们对这种普遍存在且进化上古老的修饰如何被纳入强大的表观遗传密码的认识。在这里，我们总结了目前对哺乳动物生命周期中出现的不同DNA甲基化图谱的理解，并讨论它们如何与其他调控层面相互作用以支持多种基因组功能。然后，我们回顾了人们对衰老过程中以及体细胞向癌症转变过程中发现的替代模式的兴趣日益增加的情况。随着单细胞和长读长测序技术的进步，这些领域的共同见解为将DNA甲基化的生化和遗传特征与细胞生理学、发育潜能和表型联系起来提供了新的机会。
