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 ...

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...

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...

How this scientist navigated the tough decisions and personal strain of starting a lab

How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), ...

Synthetic super-enhancers enable specific delivery of anticancer payloads, achieving tumour elimination after a single dose in a mouse model of aggressive glioblastoma.

Small changes in the non-coding part of the genome have a key role in sex determination.

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

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics suc...

AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect...

Topologically associating domains (TADs) are prominent features of genome organization. A proposed function of TADs is to contribute to gene regulation by promoting chromatin interactions within a TAD...

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