Articles in 2017

H3K4me1 is enriched at active and primed enhancers. However, whether H3K4me1 controls or simply correlates with enhancer activity and function has remained unclear. Several recent reports, including two in Nature Genetics, provide major mechanistic and functional insights into the role of H3K4me1 at enhancers.

This issue features epigenetic analysis of cell commitment at many levels in mammalian genomes: during early embryonic development, in stem cells, and in cancer cells. The establishment, propagation and dynamic robustness of cell states is addressed by comprehensive interrogation of the coordination of DNA methylation with the marks and organization of chromatin and programs of gene expression. Understanding this landscape of commitment is essential to interpretation of the functional consequences of genome variation.

What allows bacteria, both pathogens and mutualists alike, to survive in close association with a eukaryotic host? A new study performed a large-scale comparative genomics analysis to identify novel genetic and genomic traits that are enriched in plant-associated bacterial taxa.

A new study illustrates the power of the human induced pluripotent stem cell (hiPSC) platform by studying hiPSC-derived sensory neurons from 107 individuals. In addition to identifying thousands of quantitative trait loci influencing gene expression, chromatin accessibility and RNA splicing, the work highlights several underappreciated challenges in the hiPSC field.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Ron Wevers and colleagues report that mutations in the methanethiol oxidase gene SELENBP1 cause chronic extraoral halitosis. They find that enzyme deficiency leads to increased levels of methanethiol and dimethylsulfide in the breath and that knockout mice have similar biochemical phenotypes.

Analysis of 329,000 individuals in the UK Biobank identifies 116 loci associated with neuroticism. Genes implicated are enriched in neuronal differentiation pathways, and genetic correlations between neuroticism and other mental health traits are elucidated.

Rare cells resembling the 2-cell-stage embryo (2 C) arise in embryonic stem cell cultures. By performing single-cell analyses and an siRNA screen, the authors identify the intermediate cellular states and epigenetic regulators that underpin the transition to a 2C-like state.

A reference-quality genome assembly of a Drosophila melanogaster strain allows for accurate mapping of structural variants through comparative analysis with the existing Drosophila genome. Previously hidden structural variation alters a larger fraction of the genome than SNPs and often affects candidate genes underlying complex traits.

An analysis of single-cell DNA methylome sequencing data from human preimplantation embryos finds evidence for de novo methylation. Methylation reprogramming at this stage is a balance between global demethylation, which is faster in the paternal genome, and focused remethylation.

Comparative genomic analysis of 3,837 bacterial genomes, including new sequences from 484 root-associated isolates, identifies plant-associated gene clusters and plant-mimicking domains.

RNA-directed DNA methylation (RdDM) in the Arabidopsis thaliana male sexual lineage is shown here to regulate gene expression in meiocytes. Loss of sexual-lineage-specific RdDM causes mis-splicing of the MPS1 gene, thereby disrupting meiosis

The authors conduct mass spectrometry experiments identifying H3K4me1-associated proteins, including members of the BAF chromatin-remodeling complex. They show that H3K4me1 augments association of the BAF complex with enhancers in vivo and that H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex in vitro.

LeafCutter is a new tool that identifies variable intron splicing events from RNA-seq data for analysis of complex alternative splicing. The method does not require transcript annotation and can be used to map splicing quantitative trait loci.

This study identifies regulatory variants in sensory neurons derived from induced pluripotent stem cells. Despite differentiation-induced variability, an allele-specific method allowed detection of loci influencing gene expression, chromatin accessibility and RNA splicing.

Transcriptome, DNA methylome and Hi-C profiling of peri- and post-implantation mouse cell lineages identified allele- and lineage-specific methylation patterns. Global demethylation and remethylation correlate with megabase chromatin compartments.

TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit bivalent promoter hypermethylation without a corresponding decrease in gene expression in the undifferentiated state. However, PAX6 promoter hypermethylation in TKO hESCs impairs neural differentiation.