Search

An ultra-high-resolution chromatin organization map of E. coli, using Micro-C, reveals intricate chromatin structures involved in the silencing of horizontally transferred genes and those associated with active operons.

Karpinska, Zhu and colleagues characterize the structure-function relationship of the genome during cellular differentiation and demonstrate a role for enhancer-promoter interactions in gene regulation that is independent of cooperative interactions in chromatin hubs.

AcrB is a prototypical resistance–nodulation–division (RND) bacterial transporter, conferring resistance to a variety of antibiotics. HDX-MS and other, complementary approaches offer insight into AcrB structural dynamics and suggest the molecular mechanisms underlying drug export and inhibition of this multidrug-resistance conferring pump.

By applying Hi-C to cells derived from the tumors of 24 GBM patients, the authors show pervasive structural variation in GBM chromosomal organization. How such patient-to-patient variation explains the characteristic gene expression patterns in each tumor is investigated.

The mechanisms of intratumoral subtype heterogeneity in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, the authors analyse PDAC tumours and preclinical models using multi-omics and imaging; they demonstrate that AP1 dichotomy influences tumor plasticity, heterogeneity, and immune response, with potential therapeutic implications.

Using single-molecule tracking of cohesin and CTCF during zebrafish embryogenesis, the molecular kinetics underlying chromatin architecture formation was revealed and gradual emergence of chromatin structure recapitulated by polymer simulations.

Using CRISPR-guided editing, Liesenfelder et al. modify DNA methylation at epigenetic clock sites, which evokes genome-wide age-associated epigenetic modifications. Their findings suggest age-associated DNA methylation changes can be coherently modified within an epigenetic network.

XylE is a bacterial xylose transporter and homologue of human glucose transporters GLUTs 1-4. HDX-MS, mutagenesis and MD simulations suggest that protonation of a conserved aspartate triggers conformational transition from outward- to inward facing state only in the presence of substrate xylose. In contrast, inhibitor glucose locks the transporter in the outward facing state.

Planarians are model systems for stem cells and regeneration. This study provides new genome assemblies of the model species S. mediterranea and 3 relatives and uses comparative genomics of planarians to reveal that synteny is not an evolutionary constraint in flatworm genome evolution.

Members of the CHD chromatin remodeler family are implicated in human pathologies, however CHD6 remained poorly studied. Here, the authors show that CHD6 binds to and regulates autophagy and stress response genes across cell types. They identify a clinical mutation that affects its ability to recruit cofactors, leading to impaired autophagy induction and DNA repair.

The mechanisms directing chromatin remodeling complexes to genomic regions have remained elusive. Here, the authors show that lncRNAs direct SWI/SNF to cell type-specific enhancers, investigating an RNA-mediated layer of targeting specificity.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Evidence from large longitudinal neuroimaging cohorts, which include genetic and behavioral data, suggest a common neural basis for symptoms seen across multiple psychiatric disorders.

Ion mobility–mass spectrometry has enabled the study of conformation and dynamics of membrane proteins in the gas phase. Here, the enhanced flexibility of macromolecular ATPase was investigated by comparing arrival time distributions of distinct species and relating them to different solution conditions, leading to the proposal of a nucleotide-triggered regulatory mechanism.

A comprehensive map of genomic variation in melon derived from resequencing of 1,175 accessions sheds light on the population structure and domestication history of melon and agronomic traits for melon breeding.

Snyder and colleagues show global loss of promoter–enhancer connectivity during early colorectal carcinogenesis and the dependency of gene dysregulation during this process on the baseline of promoter–enhancer interaction in normal colonic epithelium.

In this study the authors utilise Hi-C, ATACseq, and RNA-seq data from 12 diagnosis/relapse matched leukemia specimens to reveal 3D genome organization as a critical factor in reshaping the transcriptional output of leukemia cells under the selective pressures of therapy.

HMGA1 helps regulate the topology of the chromatin network, supporting compartmentalization. Here, Olan et al. show that, in oncogene-induced senescence, genes are included or excluded from HMGA1 cores, suggesting HMGA1 has a fine-tuning role.

Singh and colleagues show that PDAC phenotypic plasticity is regulated via AP1 enhancer remodeling and modulated by TNF-α⁺ macrophages and pharmacological inhibition of the BRD4–cJUN–CCL2–TNF-α axis restores favorable PDAC subtypes and prognosis.

Ing et al. develop a method of establishing direct relationships between psychiatric symptoms and neuroimaging measures of brain structure and function and use it to stratify adolescent psychopathology on the basis of underlying biology. They replicate their results in independent clinical samples.

Using magnetic tweezers, Choi et al. revealed the asymmetric folding pathway of GLUT3, a human glucose transporter, suggesting the active effect of cells in helping glucose transporters overcome folding challenges when forming channels for sugar molecules.

Analyses of data from the UK Biobank reveal different urban living environments that are associated with affective, anxiety and emotional instability symptom groups and mediated by distinct neurological and genetic pathways in adults.

Using Guanidium HCl denatured glyceraldehyde 3-phosphate dehydrogenase (GAPDH), the authors provide in vitro evidence for the active involvement of the trigger factor (TF) in promoting the native folding of pre-unfolded client proteins, by preventing non-productive self-associations (misfolding) and by shielding oligomeric interfaces from aggregation.

In this Perspective, the authors present a model of assessing urban environmental factors’ impact on mental health by using UrbanSat measures and data from adolescents in the ABCD Study.

This Comment presents a high-level protocol for data harmonization within large cohorts, in which it postulates four main steps including (1) expert review, (2) pre-statistical harmonization, (3) statistical harmonization, and (4) validation.

This Comment explores new approaches to enrich large-scale population data, including incorporating macro-environmental and digital health measures.

This protocol enables the generation of human forebrain organoids from induced pluripotent stem cells with the intrinsic ability to assemble functionally integrated bilateral optic vesicles.

Integrative analyses that incorporate different levels of ‘-omics’ data represent a powerful tool for deciphering the biological mechanisms that underlie environmental influences on mental health and disease. This Comment highlights various aspects of such multi-omics approaches, using the example of the EU-funded environMENTAL project.

The focus of much of contemporary research ethics is on compliance with established protocols. However, large data-driven neuroscience research raises new ethical concerns that have no agreed-upon solution. Here we reflect on these challenges and propose better integration of public and patient involvement in this evolving landscape.