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引用次数: 0
摘要
DNA 甲基化领域已经从发现和基因组特征描述阶段成熟到寻求对这种修饰如何促进发育、衰老和疾病的更深入的功能性理解阶段。尤其是在过去的十年中,许多令人振奋的机理发现大大扩展了我们对这一古老的进化修饰如何被纳入强大的表观遗传密码的认识。在此,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化过程中发现的替代模式日益增长的兴趣。随着单细胞和长读程测序技术的进步,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、发育潜能和表型联系起来提供了新的机会。
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 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.
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