Reviews & Analysis

This Review describes the diverse roles for histone-modifying and chromatin-remodelling enzymes in mammalian differentiation. These enzymes are involved in both maintaining pluripotency and specifying cell lineage commitment. Recent progress includes their functional characterization in mouse modelsin vivoand a new appreciation of their multifaceted molecular functions.

To regulate gene expression, transcription factors must access DNA, which is organized in chromatin. This occurs on many timescales; in this Review, the authors discuss the mechanisms that underlie this interaction in regulated and stochastic processes.

Next-generation sequencing for variant identification is now becoming widespread, although pipelines have not yet been optimized. In this Perspective article, the authors discuss ways to minimize erroneous variant calls, in particular, by using replicates.

The role of epistasis in quantitative traits is controversial. This Review argues that findings from studies of these traits are consistent with pervasive epistasis and discusses how experimental designs in model organisms are used to uncover the underlying genetic interactions.

Our knowledge of the diverse types and roles of long non-coding RNAs (lncRNAs) is rapidly increasing. This Review discusses our latest understanding of lncRNAs that have validated functional roles in various differentiation and developmental processes.

Complex organismal traits, including diseases, are controlled by intricate interactions between multiple genes, intermediate molecular and cellular phenotypes, and environmental influences. This Review describes how systems genetics integrates these layers of information to provide a cohesive understanding of the molecular underpinnings of complex traits.

Bacterial whole-genome sequencing is showing promise in clinical applications. Here, the authors present their opinions on what the main bioinformatic challenges are in transferring bacterial whole-genome sequencing to medical diagnostics.

The recent improvement in technologies to identify genetic variants linked with quantitative traits has allowed the identification of variants that are associated with crop domestication. This Review considers these approaches and their application to the study of crop domestication.

Antisense transcription is increasingly being recognized as an important regulator of gene expression across all kingdoms of life and through a range of regulatory modes. Antisense transcripts are also emerging as facilitators of rapid evolution of gene regulation.

Polycomb group (PcG) proteins have long been known to have repressive functions. Recently, novel complexes of PcG proteins have been identified and have been shown to have novel molecular and biological functions, which are discussed in this Review.

Network analyses of protein–protein, genetic and drug–gene interactions have typically been limited to analyses at the whole-protein and whole-gene levels. This Review discusses how high-resolution network analyses at the domain and residue levels are providing valuable insights into diverse research fields that range from structural biology to human disease.

This Review describes how whole-genome sequencing of experimental populations of microorganisms and other species is yielding new insights into evolutionary processes. These details include variation in mutation rates, diverse genetic routes to adaptation and dynamic interactions within and between populations.

Populations of many species show phenotypic adaptations in order to maximize their fitness in local environments. This Review describes various strategies for characterizing the genomic underpinnings of these adaptations and the key findings that are emerging.

Genetic exchanges between homologous chromosomes are essential for producing haploid gametes and increase genetic diversity. Recent advances have provided insights into the mechanisms that specify recombination hot spots and the regulation of the exchange of genetic material between mammalian chromosomes.

New tools for plant biotechnology are emerging, including synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. These tools promise to expand the range of plant biotechnology applications, especially when integrated with approaches for manipulating large DNA constructs.

This Review distinguishes between three distinct routes by which similar genetic changes contribute to convergent evolution and discusses examples from diverse taxa. Convergent genetic evolution might result from the fact that some mutations both minimize pleiotropic effects and maximize adaptation.

There is an increasing realization of epigenetic dysregulation in cancer, which comprises both the mutation of genes encoding epigenetic regulators and the broader disruptions to chromatin states of the epigenome. This Review discusses our latest understanding of these phenomena, their convergence and the implications for cancer biology and therapeutics.

The recent availability of human genomic data has facilitated the search for candidate loci that are linked to adaptive human traits. This Review discusses methods and strategies for identifying these candidate adaptive loci, as well as the insights gained from applying them.

Forces are known to directly shape morphogenesis; however, the role of forces in activating cell signalling in cell fate transitions is less well understood. In this Review, the authors consider the role of mechanics in developmental transitions and propose areas for future study.

The recent proliferation of omics data has required a toolbox of integrative systems biology bioinformatics approaches to elucidate functional relationships between molecules. Here the authors explain the principles behind these approaches and discuss their applications.