Classifying chromatin loops from 3D genomics data according to their epigenetic and structural attributes is important for inferring their functional roles. Currently, such classification typically relies on the manual intersection of epigenomic signal peaks and loop anchor locations. To automate this, remove peak-calling biases and include information inherent to 3D genomics signal structure, we developed LoopBin, a framework based on a variational deep embedding (VaDE) neural network. We applied LoopBin to kilobase-resolution Micro-C data and segmented tens of thousands of loops into clusters with distinct features using minimal histone modification and transcription factor-binding data. These features were indicative of apparently distinct biological function by each subgroup of loops. Therefore, LoopBin can provide insights into the dynamic shifts in loop classification that can occur upon perturbation of cell homeostasis or signaling. ### Competing Interest Statement The authors have declared no competing interest.

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.

Chromosomes unfold and refold each time cells divide. A study by Schooley et al. demonstrates that chromosome-intrinsic and cytoplasmic factors uniquely contribute to interphase chromosome structure, ...

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitatin...

Estell and Łazowski et al. show that Integrator and Restrictor form distinct pathways for early attenuation of RNA polymerase II: Integrator acts at the promoter-proximal pause site, whereas Restrictor acts over a downstream “restriction zone.” For transcription to proceed, CDK7/9 oppose Integrator, while U1 snRNP counteracts both Integrator and Restrictor.

Nature Reviews Molecular Cell Biology, Published online: 03 November 2025; doi:10.1038/s41580-025-00924-2Siyuan (Steven) Wang discusses a 1984 study that reported that transcriptional regulation (in this case, in bacteria) depends on the formation of DNA loops.

Nature Structural & Molecular Biology, Published online: 17 October 2025; doi:10.1038/s41594-025-01687-2Goel et al. produce high-resolution three-dimensional genome structure mapping from mitosis to G1 phase to show unseen interactions between enhancers and promoters in prometaphase. Polymer modeling indicates the interactions are facilitated by chromosome compaction.

Genome inheritance during cell divisions relies on replicated sister DNAs being connected by cohesin rings. Minamino et al. reconstitute sister chromatid cohesion establishment during DNA replication using purified budding yeast proteins. The experiments yield molecular insight into more than one way in which sister chromatid cohesion can be built.

We have investigated changes in chromosome conformation, nuclear organization, and transcription during differentiation and maturation of control and mutant motor neurons harboring hexanucleotide expa...

During development as cells exit a pluripotent state, chromatin looping interactions are strengthened, but the mechanism for this is unknown. A study now shows that CTCF–RBP interactions increase upon differentiation of embryonic stem cells to neural stem cells, and that the non-coding RNA Pantr1 collaborates with CTCF and RBPs to contract the genome.

Wang et al. show that the architectural protein LDB1 forms a complex with single-stranded DNA-binding proteins (SSBPs) in vitro and in vivo. SSBP3 stabilizes LDB1 self-interactions to support chromatin loop formation.

In a recent Nature article, Zhang et al. develop a non-natural micropeptide killswitch that modulates the material properties and biomolecular composition of target condensates, enabling direct regulation of cellular processes in condensatopathies.

Bremer et al. compare two competing models for how transcription factors mediate gene regulation: via phase separation or via soluble complex formation. They demonstrate that Gcn4 sequence variants can function as soluble complexes as well as heterotypic condensates but that condensates formed by variants with high affinities can dampen activities.

Nature Reviews Genetics, Published online: 30 June 2025; doi:10.1038/s41576-025-00862-xDisruption of the 3D genome caused by structural variation contributes to developmental disorders and cancer. The authors review the causes and molecular and clinical consequences of position effects arising from disruptions to the genome architecture.