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Programmable nucleases — including ZFNs, TALENs and RGENs derived from the prokaryotic CRISPR–Cas system — enable targeted high-precision genome engineering. This Review summarizes current knowledge of nuclease-specific features, individual pros and cons, and approaches to improve the efficiency of these enzymes to help researchers to choose the most appropriate tool for various genome editing experiments and applications.
This Review describes how genomic technologies are providing novel insights intoMycobacterium tuberculosis, which is the causative agent of human tuberculosis. There has been progress in understanding the ancient evolutionary history of human-adapted M. tuberculosis, mutations underlying strain diversity and drug resistance, and the host–pathogen molecular interactions.
Diverse types of RNA in various species are modified by methylation to formN6-methyladenosine (m6A). This Review describes how progress in the characterization of m6A distributions and of proteins that 'write', 'erase' and 'read' this mark is revealing roles for reversible m6A methylation in dynamic gene expression control.
Enhancers are DNA elements that are key regulators of gene expression, but their complexities and context dependence makes their identification and characterization challenging. This Review discusses how an improved understanding of the varied properties of enhancers is being used in diverse approaches for the systematic prediction of enhancers genome wide.
This Review discusses cryptic genetic variation and focuses particularly on empirical support for widespread cryptic genetic variation in natural populations, its potential role in human diseases and its contribution to evolution.
CCCTC-binding factor (CTCF) is a DNA-binding protein that has various, often seemingly contradictory, roles in gene regulation. This Review describes these disparate functions and how the context-dependent looping of DNA regions by CTCF is emerging as a potential unifying mechanism that underpins these diverse roles.
Increasing evidence suggests crucial functions for histone variants in diverse biological processes. This Review examines the roles of histone variants in mammalian germ cell and embryonic development, as well as the consequences of their aberrant regulation in human disease.
The rate and mechanisms of evolution of transcription factor binding show striking differences across diverse metazoan phyla. This Review highlights insights gained from sequence-based comparisons of genomes and ChIP–seq studies analysing the evolution of transcription factor binding, as well as their conceptual contribution to models of regulatory evolution and gene expression control.
Genomic approaches are an increasingly important aspect of speciation research. The authors review recent insights from speciation genomics and propose a roadmap for this field, which is aimed at addressing both long-standing and emerging questions about speciation.
Recent advances in bioinformatics, proteomics and high-throughput analyses of translation have begun to uncover short open reading frames (sORFs) with coding potential. This Review considers unifying characteristics of these sORFs, methods to identify them and potential functions of the resultant short peptides.
The cellular transcription, mRNA processing and export machineries seem to have co-evolved to allow spatiotemporal coupling of these processes. Here, the author reviews recent insights into the relative amount of co-transcriptional and post-transcriptional processing, the relationship between mRNA elongation and processing, and the regulating role of the carboxy-terminal domain of RNA polymerase II.
There continues to be active debate about the timings, locations and details of various events in human population history. This Review describes how whole-genome sequencing of modern and ancient humans has complemented more traditional methods to provide valuable historical insights.
Ribosome profiling is a recently developed technique that uses deep sequencing to study translationin vivo. This approach has provided new insights into the identities and amounts of proteins produced by cells, as well as into the mechanism of protein synthesis itself.
The derivation of disease-relevant cell types from pluripotent stem cells holds much promise for disease therapy. The recent progress in directed differentiation and the challenges ahead are discussed in this Review.
Methods that are based on next-generation sequencing technology are used for a range of applications from genome sequencing to transcriptomic and epigenomic studies. Here, the authors discuss the important issue of sequencing depth in the design of such experiments.
Constraint-based modelling methods systematize biochemical, genetic and genomic knowledge into a mathematical framework, which enables a mechanistic description of metabolic physiology. Recent successes in using this approach have implications for microbial evolution, interaction networks, genetic engineering and drug discovery.
In the past few years, there have been rapid advances in the identification of the genetic components of autism spectrum disorders, particularly in the form ofde novomutations. Here, the authors review these developments in light of genetic models for autism spectrum disorders.
