Volume 20 Issue 5, May 2019

Variants of unknown significance (VUS) are genetic variants whose association with disease risk is unknown. The authors posit that VUS should not inform clinical decision-making as the benefits of returning this genetic information to patients undergoing genetic testing are outweighed by the potential for harm.

Two studies report substantial temporal and spatial variability in mutagenic signatures caused by APOBEC cytidine deaminases in cancer.

Two studies in Science show that cytosine base editors, but not adenine base editors or CRISPR–Cas9, induce notable off-target single-nucleotide variants in rice and in mouse embryos.

A study in Nature reveals that N⁶-methyladenosine (m⁶A) modification of RNA occurs co-transcriptionally and is mediated by interactions between histone H3 lysine 36 trimethylation (H3K36me3) and the m⁶A methyltransferase complex.

Nair et al. contrast events at specific super-enhancers after acute and chronic ligand-induced activation and show that biomolecular condensates at these enhancers undergo physical changes over time that affect chromatin conformation and gene expression.

The functional interpretation of single-cell RNA sequencing (scRNA-seq) data can be enhanced by integrating additional data types beyond RNA-based gene expression. In this Review, Stuart and Satija discuss diverse approaches for integrative single-cell analysis, including experimental methods for profiling multiple omics types from the same cells, analytical approaches for extracting additional layers of information directly from scRNA-seq data and computational integration of omics data collected across different cell samples.

Single-cell RNA sequencing (scRNA-seq) enables transcriptome-based characterization of the constituent cell types within a heterogeneous sample. However, reliable analysis and biological interpretation typically require optimal use of clustering algorithms. This Review discusses the multiple algorithmic options for clustering scRNA-seq data, including various technical, biological and computational considerations.

Eukaryotes differ substantially from bacteria and archaea owing to their nucleosome-based packaging of DNA. In this Review, Talbert, Meers and Henikoff place gene regulation in an evolutionary context by discussing how the emergence and diversification of eukaryotic chromatin provided both challenges and opportunities for intricate mechanisms of gene regulation in eukaryotes.

In this Timeline article, Shay and Wright provide a historical account of progress in our understanding of telomeres (the ends of linear chromosomes) and telomerase (the primary enzyme that maintains and extends telomere lengths). Their perspective covers seminal moments from the early discoveries through to our latest understanding of the roles of telomeres and telomerase in ageing, diverse human diseases and gene regulation.