An exciting postdoctoral position is available to research the role of epigenetic marks in gene regulation.

This Review discusses how rare-disease-causing variants in the noncoding genome impact gene regulation, why these examples are so few and how new approaches could accelerate discovery of noncoding var...

Development depends on gene regulation by enhancers across long genomic distances. This Perspective discusses mechanisms enabling long-range enhancer–promoter communication and the potential advantage...

Cees Dekker Lab

Isoforms are seldom considered in genetic variant interpretation. Here the authors map common and rare variants to alternative isoforms, which can be highly expressed and tissue-specific. A common DPP...

Isoforms are seldom considered in genetic variant interpretation. Here the authors map common and rare variants to alternative isoforms, which can be highly expressed and tissue-specific. A common DPP...

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

Author summary Individual humans show widely varying responses to viral infection, including from SARS-CoV-2, which causes COVID-19. Part of this variation is driven by host genetic factors, where gen...

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...

Nature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...

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...

This study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

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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

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...

Acute depletion of NIPBL reveals a class of chromatin loops that are independent of NIPBL for their maintenance but not their establishment and that NIPBL is necessary for the expression of lineage-de...

Facial development is highly sensitive to genetic and environmental perturbation, with craniofacial malformation associated with over one-third of congenital birth defects. The face arises during an early and largely inaccessible window of embryonic development, with a large contribution from transient and multipotent cranial neural crest cells (CNCCs). Assessment of the molecular and cellular mechanisms driving normal and disordered human facial development therefore relies greatly on the use of in vitro cellular models. Here, we adapted a neurosphere-based CNCC differentiation protocol to facilitate robust quantification of early specification and migration events. Introduction of single-cell aggregation with arrayed plating enabled standardisation of neurosphere size, growth and patterning. Inclusion of fibronectin coating enhanced the efficiency of neurosphere attachment and synchronicity of CNCC migration timing. To demonstrate application of the Array-CNCC method, we developed a strategy for mosaic co-culture, which can facilitate differentiation of wildtype untreated cells directly alongside cells exposed to distinct drug treatments or genetic alterations. Finally, we present a screening approach which we use to test the impact of distinct extracellular matrix components on neurosphere morphology, CNCC migration and gene expression. Together, the Array-CNCC method is highly amenable to quantitative phenotyping and screening approaches, enabling enhanced craniofacial disease modelling with both cellular and molecular readouts. ### Competing Interest Statement The authors have declared no competing interest. Medical Research Council, MC\_UU\_00035/12, MC\_ST\_00035 Wellcome Trust, https://ror.org/029chgv08, 227712/Z/23/Z

This collection summarizes key aspects of our current experimental and theoretical understanding of eukaryotic genome folding and its relationship with the molecular processes governing cell fate. Ove...

Nature Communications - The type I interferon response is suppressed during early development, making embryos susceptible to pathogens. Here, the authors show that this suppression contributes to...