Distal regulatory elements (DREs), such as enhancers, can regulate genes across megabase-long distances, presumably via coming into close spatial proximity. The establishment of new transcriptional programmes during cell type transitions is associated with widespread rewiring of the spatial organisation of the genome, including gain and loss of chromatin interactions. Extensive effort has been invested into understanding how chromatin interactions are formed during development, yet the mechanisms underlying their developmental loss remain largely unclear. By leveraging chromatin accessibility-assisted footprinting, acute protein degradation and chromatin conformation capture, we show that loss of promoter interactions cannot be explained by reduced binding of sequence-specific transcription factors (TFs). Instead, we identify a subset of interactions that depend on cohesin for programmed developmental disruption. These sites are characterized by high Polycomb enrichment and TF occupancy and engage in strong long-range interactions that undergo extensive differentiation-dependent rewiring. Preventing interaction loss by acute cohesin degradation results in the preferential downregulation of associated genes. Together, these results suggest that cohesin indirectly regulates developmental loss of Polycomb interactions by enabling the acquisition of other potentially regulatory contacts in a process that may shape transcriptional programs during cell type transitions. ### Competing Interest Statement The authors have declared no competing interest. European Research Council Helmholtz Society, VH-NG-1604

DNA methylation is an important epigenetic mechanism involved in gene regulation. Most methods focus on analysing DNA methylation averaged from multiple reads, yet these average methylation profiles o...

View details and apply for this Postdoctoral Training Fellow - Chromatin Biology and Epigenetics vacancy in Chelsea . Salary: Salary range £45,600 - £51,450 per annum. Dependent on re...

Zhao et al. describe an enhancer-dense nuclear microenvironment in the cerebellum that includes long neuronal genes and mega-enhancers. This microenvironment partly depends on the transcription factor...

The roles of transposable elements in primate brain development remain underexplored. Here, the authors identify transposable elements with ancestral regulatory potential that have been co-opted as ci...

An encyclopedia of more than 92 million enhancer–gene regulatory interactions created as part of the ENCODE4 project provides a valuable resource for future studies of gene regulation and human geneti...

This study uses a precise and efficient clustered regularly interspaced short palindromic repeats (CRISPR) prime editing system to substitute lysine residues in histone H3, individually or in combinat...

Cis-regulatory elements, such as enhancers, play an essential role in coordinating gene expression programs during cellular transitions. As such, substantial efforts have been made to characterize enh...

Integration of gene expression data from multiple tissues across four mammalian species reveals conserved transcriptomic signatures of mammalian ageing and mortality and uncovers the modular...

Stem cell identity and differentiation require precise gene regulation, yet key regulatory components remain poorly understood. Here, the authors show that variant U1 snRNAs have distinct and essentia...

How host organisms adapt their defense systems to newly invading transposable elements remains poorly understood. Here, we show how Drosophila melanogaster acquired PIWI-interacting RNA (piRNA)-mediat...

Come to this beautiful Swedish inland scenario to learn the most advanced technologies to study transcriptional regulation.

Background The ability to deposit histone H3K27-trimethyl (me3) marks is essential for transcriptional repression by Polycomb Repressive Complex 2 (PRC2). This is largely attributed to Polycomb repres...

Alternative splicing patterns have diverged rapidly during vertebrate evolution. By integrating genome-wide predictions of stable RNA duplexes, alternative splicing profiles, and proximity ligation-de...

Long‑range chromosome encounters in cells are hard to quantify. Here, the authors induce artificial contacts in yeast and show that intra‑chromosomal interactions form faster than inter‑chromosomal on...

CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 637587, 865459 Dutch Research Council, https://ror.org/04jsz6e67, 016.161.316, VI.C.222.049 Dutch Cancer Society, https://ror.org/0368jnd28, N/A

Abstract. Mitotic fidelity requires proper chromosome alignment at the spindle equator, a process known as chromosome congression, mediated by well-establi

Molecular Genetics and Genomics - Transposable elements (TEs) are critical contributors to gene regulatory networks, yet their repetitive and abundant nature complicates efforts to elucidate their...

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SRCAP depletion causes rapid replacement of H2A.Z by H2A, leading to upregulation of lineage-specific transcription factors. SRCAP also prevents pioneer transcription factor binding by steric hindranc...

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...

Background Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Results Here, we report a catal...

Abstract. The type I interferon (IFN) response is the main innate immune pathway against viruses in mammals. This pathway must be tightly regulated to prev

Some proteins mimic the repressive mark H3K27me3, but the physiological relevance of this phenomenon was unclear. Agius et al. show that the PRC2 subunits JARID2 and PALI1 mimic H3K27me3 to antagonize...

Nature Structural & Molecular Biology - METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining...

LINE-1 (L1) retrotransposition generates somatic genomic variation in human cancer, but short-read sequencing has limited our understanding of its structural consequences and dynamics. Using long-read...