Nature Genetics - Pierre Chambon (1931–2026)

Proteins with intrinsically disordered regions (IDRs) migrate at a higher apparent molecular weight in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, complicating their analysis and...

The term ‘housekeeping gene’ evokes a sense of banality. These are the boring genes that hum in the background, impervious to cell state or stress. For a developmental biologist captivated by the impa...

Core promoters are sites where transcriptional regulatory inputs of a gene are integrated to direct the assembly of the preinitiation complex (PIC) and RNA polymerase II (Pol II) transcription output....

Highly conserved mRNA 3′ UTRs act as co-translational chaperones for intrinsically disordered regions (IDRs), preventing inter-domain misfolding and enabling biogenesis of fully active proteins.

How intrinsically disordered regions (IDRs) shape chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We used proximity-assisted photoactivation (PAPA), a single...

Cell viability depends on the precise expression of essential genes, which are controlled by CpG-island (CGI) promoters densely bound by transcription factors (TFs). This has led to the prevailing model that TFs cooperate to ensure ubiquitous expression. Here, using rapid and reversible single and combinatorial degradation in murine stem cells, we systematically dissect the regulatory interactions between five key TFs. We uncover an unexpectedly specific architecture in which regulatory dominance, rather than cooperation, is the prevailing mode, where individual TFs autonomously drive chromatin opening and gene activation at largely distinct promoters. Cooperative regulation occurs at a minority of sites with antagonistic or synergistic outcomes modulated by the interplay between nucleosome positioning and TF sensitivity to chromatin. This logic is recapitulated at synthetic sequences and reflected in human genetic variation. These findings reveal that single TFs dominantly activate distinct sets of CGI-linked genes, including essential genes, across development, homeostasis, and disease. ### Competing Interest Statement The authors have declared no competing interest. DFG, GR 6341/2-1, 556634773

SAGA regulates gene expression through KAT2A‑mediated acetylation, but how KAT2A stability is controlled was unclear. Here, the authors show that SAGA CORE subunits stabilise KAT2A, and that unassembl...

Nature Methods - AF2BIND is a logistic regression model trained on AlphaFold2 pair features to predict small-molecule binding-site residues in proteins, without multiple sequence alignments,...

Here proteomic chromatome analysis shows metabolic enzymes widely localize to chromatin in cancer in a tissue-specific manner. Nuclear enzymes affect DNA damage/repair and transcription, revealing non...

Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmica...

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics suc...

Chromatin organization, through the assembly of DNA with histones and the folding of nucleosome chains, regulates DNA accessibility for transcription, DNA replication and repair. Although models deriv...

CHD4 directly limits transcription factor binding to chromatin, which prevents activation of silent or cryptic enhancers but facilitates activity of active enhancers.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

Transcription factors (TFs) are traditionally classified as activators or repressors, yet some can perform both roles. We highlight well-supported examples of dual activator/repressor functions and...

This study reconstructs the gene regulatory networks that define cell types in the sea anemone Nematostella vectensis, providing a valuable resource for comparative regulatory genomics and the evoluti...

Nature Ecology & Evolution - Analysis of the 3D chromatin architecture and cis-regulatory elements in a sea urchin and a sea star reveals mechanisms of 3D chromatin organization in echinoderms...

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types...

Mammalian SWI/SNF chromatin remodeling complexes modulate DNA accessibility and gene expression; however, their genomic targeting mechanisms remain incompletely understood. Here, we identify SWIFT (SW...