Articles in 2020

H3K27ac HiChIP analysis helps to identify promoter-interacting expression quantitative trait loci (pieQTLs) in five common immune cell types. Some pieQTLs overlap with nontranscribed promoters that act as enhancers.

WAPL creates a pool of free cohesin that binds to cell-type-specific sites. This cohesin turnover is important for maintaining promoter–enhancer loops.

A multivariate genome-wide association study identifies 203 signals associated with facial variation. These signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues.

A resource of cell-type-specific IMPACT regulatory annotations improves the trans-ancestry portability of polygenic risk scores by prioritizing variants enriched for trait heritability.

Recent progress relating to the catalytic and non-catalytic functions of histone modifying complexes warrants a fresh look at the role of histone modifications and the “histone code” model.

Maintaining ignorance to self-nucleic acids can prevent inflammatory diseases such as Aicardi–Goutières syndrome (AGS). A new study finds that mutations in LSM11 and RNU7-1, which encode components of the histone messenger RNA–preprocessing complex, cause AGS by loosening the binding of cyclic GMP–AMP synthase (cGAS) to nucleosomes, thus enabling cGAS activation and induction of type I interferons.

Harmonized analysis of 1,048 melanomas shows different global genomic properties among subtypes and identifies subtype-specific enrichment for secondary driver genes.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA–processing complex, cause an autoinflammatory syndrome due to enhanced interferon signaling mediated by the cGAS–STING pathway, showing an essential role for nuclear histones in suppressing the immunogenicity of self-DNA.

Enhancer variants associated with red blood cell traits alter signaling transcription factor motifs, leading to changes in expression of genes that are upregulated during erythroid differentiation.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

PolyFun is a computationally scalable framework for functionally informed fine-mapping that makes full use of genome-wide data. It prioritizes more variants than previous methods when applied to 49 complex traits from UK Biobank.

MLL4 (KMT2D) loss of function, as found in Kabuki syndrome, affects the chromatin compartmentalization of Polycomb proteins and changes the nuclear architecture. Inhibition of ATR reestablishes mechanosignaling of mutant mesenchymal stem cells and their commitment to becoming chondrocytes.

On 16 September 2020, when the news of José Luis Gómez-Skarmeta’s untimely passing broke, the scientific community was left in dismay.

A BAH module in BAHCC1 recognizes H3K27me3 and is involved in gene silencing. BAHCC1 is highly expressed in acute leukemia cells and contributes to their proliferation.

Phased diploid genomes of the cultivated apple Malus domestica cv. Gala and its two major wild progenitors M. sieversii and M. sylvestris, as well as pan-genome analyses, provide insights into the genetic history of apple domestication.

Given an opportunity to chronicle the experience of traversing America as a Black man, I elect to convey a less frequently told vantage point. This is the perspective of the ‘accomplished’ bootless.

Patterns of co-occurring and mutually exclusive mutations reveal synergistic interactions among cancer driver genes. A new study functionally confirms these interactions and builds the pairwise relationships into networks of pathway disruption that have better predictive power than specific mutations alone.

In a classical view of carcinogenesis, carcinogens directly cause mutations. In this issue, Riva et al. explore the effects of 20 known or suspected human carcinogens and find discernible mutational signatures for only three of them.