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Recent drug discovery efforts in cancer have focused on epigenetic marks, such as DNA methylation and histone modifications. The authors discuss existing therapeutics that target the cancer epigenome, the role of epigenetic marks as biomarkers of drug response and emerging strategies that combine epigenetic drugs with other cancer therapies.
This Timeline article reviews the evolution of both prenatal and pre-implantation genetic testing, from their historic origins to ongoing development and implementation of tools for genome-wide single-cell and cell-free fetal DNA analysis. Future developments and some of the ethical issues that arise from these new technologies are also discussed.
Formal representations of Waddington's epigenetic landscape represent cell fate decisions as smooth, continuous events in which cells follow predetermined trajectories. Here, the authors provide an alternative interpretation and posit that fate decisions are discontinuous, stochastic events within cell lineages.
Numerous long non-coding RNAs (lncRNAs) have emerged as having important and mechanistically diverse roles in gene regulation. However, for most lncRNAs, evolution is rapid and functions remain uncharacterized. This Review describes how comparative genomics and transcriptomics can provide broad insights into the functional importance and evolutionary trajectories of lncRNAs across species, and offers guidance for cross-species studies of lncRNAs.
In early germline development, extra-embryonic signals trigger a regulatory network that induces the specification and subsequent epigenetic reprogramming of primordial germ cells, the precursors of sperm and eggs. Here, the authors review germline specification and reprogramming in humans, and discuss the crucial mechanistic differences between these processes in humans and mice.
Precision medicine is a strategy for tailoring clinical decision making to the underlying genetic causes of disease. This Review describes how, despite the straightforward overall principles of precision medicine, adopting it responsibly into clinical practice will require many technical and conceptual hurdles to be overcome. Such challenges include optimized sequencing strategies, clinically focused bioinformatics pipelines and reliable metrics for the disease causality of genetic variants.