Abstract. The evolution of de novo genes from ancestrally nontranscribed sequences has been reported in a wide range of taxa. However, the DNA sequence cha

Scientists are poking holes in established ideas about how cells live and die, and are harnessing these discoveries to fight diseases from cancer to autoimmune conditions.

Super-enhancers have been proposed to cluster in the nucleus when compared to other genomic elements. Le et al. found that super-enhancer clustering was rare and driven by non-specific interactions. P...

Can we epigenetically alter our way out of stroke risk? This new study suggests it might be possible: a one time RNA edit silences the the clotting protein ITGB3 in stem cells, and that silencing carr...

The Review describes shared ancient, conserved mechanisms between human antiviral immunity and bacterial anti-phage systems, outlining universal principles of pathogen sensing, signalling and effector...

Nature Reviews Genetics, Published online: 23 July 2026; doi:10.1038/s41576-026-00991-xGenetic variation influences biological processes across scales; however, deciphering how effects propagate from molecules to whole organisms remains a key challenge in human genetics. In this Review, Laman Trip and Beltrao discuss how to link genetic variation to mechanisms across interacting biological levels using network, single-cell and imaging approaches.

Aygenli et al. map chromatin-bound CLOCK/BMAL1 protein complexes across three mouse tissues and uncover PROX1, HNF1B and HOXA5 as homeodomain cofactors that directly bind and co-occupy BMAL1 sites to ...

Zhu et al. characterize how the transcriptional regulator BRD4 interacts with acetylated nucleosomes. Their cryo-EM structure shows that the first bromodomain of BRD4 binds both the acetylated histone H4 tail and nucleosome DNA. Unexpectedly, BRD4 does not need histone acetylation to bind nucleosomes with high affinity in vitro.

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 tran...

Large-scale chromatin compaction quantitatively predicts the percentage of cells with durable epigenetic memory of gene silencing.

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 bindi...

Housekeeping genes maintain robust expression across cell types despite dynamic transcription factor fluctuations, yet their haploinsufficiency is associated with many tissue-specific developmental di...

A resource of human RNA-protein associations is produced using a sequencing-based method.

Ultra-weak ‘biophotons’ might be used to diagnose disease, or could even represent a new signalling mechanism in cells.

This study introduces iChIP2, a low-input chromatin immunoprecipitation followed by sequencing method that profiles histone post-translational modifications (hPTMs) simultaneously across diverse eukar...

Nucleosome spacing influences higher-order chromatin fiber organization in vitro but how this relates to cellular chromosome structure remains contentious. To address this, we developed Ligation Analy...

Nature Cell Biology - A study shows that TEAD1 can form both active and inactive condensates. Small condensates at enhancers or promoters promote transcription, whereas large condensates at...

During regeneration, tissues must translate transient cellular variability into stable spatial organization. Tissue architecture generates a density-dependent window of heterogeneity in the mechanosen...

Enhancers activate specific target promoters, but whether intrinsic enhancer-promoter compatibility contributes to this specificity is debated. Recent studies using different reporter assays have reac...

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

An analytical pipeline called Iteratively Defined Lengths of Inaccessibility (IDLI) maps the genome-wide occupancy of a range of nucleosome types and shows that most nucleosomes exhibit programmed ‘di...

Nature Cell Biology - Kukreja et al. show that blocking cell division in zebrafish does not affect differentiation of major cell types during gastrulation and segmentation, but it does decelerate...

A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor bind...