Volume 51 Issue 9, September 2019

Far from being junk DNA, the pervasive retrotransposons that populate the genome have a powerful capacity to influence genes and chromatin. A new study demonstrates how the transcription of one such element, HERV-H, can modify the higher-order 3D structure of chromatin during early primate development.

Inferring adaptation, migration and population history would be profoundly easier if we could use the genomes that we sequence to infer the true genealogical history of each locus. Two new papers bring us close to achieving this goal.

A mutation in RAS oncogene family-like 3 (RABL3) is discovered in a family with multiple cases of pancreatic cancer. Zebrafish modeling and biochemical approaches suggest that truncated RABL3 elevates KRAS activity via accelerated prenylation.

Genomic analysis of 906 Clostridium difficile strains shows that this enteropathogen is undergoing speciation, which is linked to the selection of genes involved in sporulation and in the metabolism of simple dietary sugars.

Relate is a new method for evolutionary analysis of large genetic datasets that can estimate branch lengths, mutational ages and variable historical population sizes.

A new method for inferring genealogical histories from large-scale genetic data is used to characterize population structure using data from the 1000 Genomes Project, the UK Biobank and the Simons Genome Diversity Project.

Systematic analyses of large-scale genome-wide association data provide an overview of pleiotropy and genetic architecture for hundreds of human complex traits and diseases.

An approach to estimate the contribution of all alleles to phenotypic variation is applied to transcription regulation using whole-genome sequencing and transcriptome data. Ultrarare variants contribute approximately 46% of cis heritability across genes.

Single-cell DNA replication profiling shows that A/B compartments change coordinately with replication timing (RT) during mouse embryonic stem cell differentiation, with B to A changes preceding late to early RT changes and transcriptional activation.

A new technique called NET-CAGE identifies 5′ ends of nascent RNAs with high sensitivity, including enhancer-derived RNAs. This approach shows that enhancer–promoter pairs are generally activated simultaneously.

Genetic deletion or transcriptional silencing of HERV-H elements in human pluripotent stem cells (hPSCs) eliminates nearby topologically associating domain boundaries, while de novo insertion of HERV-H elements can introduce new ones. Mutations of specific HERV-H elements can impact hPSC differentiation.

Transcriptional profiling of 61,052 cells undergoing epithelial-to-mesenchymal transition (EMT) shows continuous waves of gene regulation, not discrete stages. A CRISPR screen orders EMT regulators along EMT progression.

The authors generate cell lines deficient for 22 BAF subunits, studying effects on complex composition, chromatin accessibility and gene expression. They identify synthetic lethal interactions between SMARCA4–ARID2, SMARCA4–ACTB and SMARCC1–SMARCC2.

The first annotated chromosome-level reference genome assembly for pea, Gregor Mendel’s original genetic model, provides insights into legume genome evolution and the molecular basis of agricultural traits for pea improvement.