A large-scale functional screen identified noncoding variants that regulate gene activity during human brain development, providing insights into the molecular mechanisms that shape differences in hum...

The genomic regions regulating gene expression are often themselves transcribed into a variety of noncoding RNAs (ncRNAs). However, the regulatory roles of this noncoding transcription remain largely ...

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...

2-cell like cells (2CLC) are a transiently cycling population of cells with totipotent-associated features. Although CTCF depletion induces 2CLC conversion in mouse ESC, whether this reprogramming is ...

Spermatogonial stem cells (SSCs) maintain male fertility, but how their clonal dynamics change with age remains poorly understood. Here, we use in vivo CRISPR barcoding in zebrafish to label SSCs and ...

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...

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...

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Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity ...

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

Ostendorf et al. show that activation of liver-X-receptors preconditions T cells to render them more receptive to adopting effector states upon activation.

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.

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...