DNA 甲基化领域已经从发现和基因组表征阶段发展到寻求更深入地了解这种修饰如何影响发育、衰老和疾病的功能阶段。特别是，过去十年出现了许多令人兴奋的机械发现，这些发现极大地扩展了我们对如何将这种通用的、进化上古老的修饰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一生中出现的独特 DNA 甲基化景观的理解，并讨论了它们如何与其他调控层相互作用以支持不同的基因组功能。然后，我们回顾了人们对衰老和体细胞向癌症转变过程中发现的替代模式日益增长的兴趣。除了单细胞和长读长测序技术的进步之外，这些领域的集体见解也为将 DNA 甲基化的生化和遗传特征与细胞生理学、发育潜力和表型联系起来提供了新的机会。© 2024。Springer Nature Limited。

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.© 2024. Springer Nature Limited.