Research articles

This study uses single-molecule footprinting to quantify chromatin accessibility at enhancers and promoters in mouse embryonic stem cells and to dissect the contributions of transcription factor binding and chromatin context.

The authors present INCOMMON, an open-source Bayesian inference tool that determines the multiplicity and copy number of driver mutations from tumor sequencing datasets.

The spatial organization of human kidney development is explored using single-cell RNA sequencing and spatial transcriptomics, highlighting the crucial role of microenvironmental signals in guiding cell fate.

Multi-ancestry genome-wide association analyses of Hashimoto’s thyroiditis identify new risk loci and highlight shared genetic architecture with other autoimmune diseases and pleiotropic effects on clinical outcomes.

This study uses a mouse model of inflammatory bowel disease to explore how mutations and cellular context combine to drive the transition to malignancy.

Genome-wide analyses in up to 121,579 pregnant women from China identify genetic associations across 111 phenotypes, including gestation-specific effects and interactions with gestational timing.

This study reports genetic effects on mass spectrophotometry-based plasma proteomics in a cohort of ~1,400 British South Asians, accessing parts of the proteome missed by other proteomics platforms. The resulting protein quantitative trait loci are integrated with genome-wide association study data to find potential mechanisms of disease.

Intrinsically disordered regions impose regulatory restraints on gene-activating demethylases, limiting chromatin engagement and preserving genomic stability. This function is a key determinant of the distinct substrate preferences and regulatory activities of FTO and ALKBH5 in mammals and plants.

A pangenome of tetraploid wheat constructed from 12 de novo genome assemblies spanning 10 subspecies, integrating with whole-genome sequencing data, highlights genetic variation associated with agricultural traits.

Pangenome analyses of chromosome-scale genome assemblies for 125 diverse cucumber accessions highlight structural variation shaped by selection for geographical adaptation, fruit-length diversification and disease resistance.

This study uses a highly selective inhibitor to elucidate DNMT1’s specific functions and their regulation. Notably, RFN4-mediated SUMOylation enhances DNMT1 mobility and DNA methylation, thereby promoting the suppression of endogenous retroviral element-dependent viral mimicry.

By inserting diverse promoters at the mouse Sox2 locus, Koska et al. show that promoter strength, position and transcript length tune promoter competition through transcription-dependent insulation, independent of CTCF/cohesin, while HUSH silencing counteracts the effect.

Genome-wide association analyses identify risk variants for borderline personality disorder and find genetic correlations with psychiatric disorders, behavioral traits and somatic diseases.

Tractor-Mix is a GWAS method for admixed cohorts with high relatedness, improving ancestry-specific effect estimation, controlling false positives and boosting power to detect ancestry-enriched loci across diverse populations.

Analyses in prostate cancer cell lines show that FOXA1 mediates tissue-specific recruitment of NIPBL to chromatin to orchestrate three-dimensional genome organization, acting in concert with ETS1 and other pioneer transcription factors.

Tünnermann et al. use live-cell imaging to study promoter activity under the control of an enhancer inserted at different genomic distances. RNA production from the promoter occurs in clusters of transcriptional bursts whose frequency is dictated by enhancer distance.

This study examines interactions between polygenic scores and pairs of environmental contexts across seven diseases and introduces the proportion needed to benefit as a metric to quantify the expected effectiveness of interventions as a function of polygenic risk.

SelectSim uses cancer and healthy tissue sequencing datasets to identify co-mutations that occur more or less frequently than would be expected by chance. Differences in co-mutation patterns observed during different stages of tumor evolution are also explored.

The study integrates cross-species single-cell and genomic analyses with functional validations to map the endosteal bone compartment, revealing musculoskeletal-disease-relevant cell types and transcriptional programs.

A graph-based mung bean pan-genome created using genome assemblies for 11 representative wild and cultivated accessions highlights a vast catalog of structural variations and their functional impact on agronomic traits.