Noncoding regulatory elements in the human genome can control gene expression through distinct mechanisms, including acting as enhancers, silencers, or topological elements. However, we lack tools to ...

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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 ...

Simulations integrating micro-C and imaging data provide a coherent view of chromatin organization from nucleosomes to clutches to domains, revealing that most regions form compact domains but short r...

![GRAPHICAL ABSTRACT][1]</img> GRAPHICAL ABSTRACT Crosslinking and immunoprecipitation followed by sequencing (CLIP-seq) is widely used to identify the RNA targets of RNA-binding proteins (RBPs). H...

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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...

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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

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-R …

Key PointsMECOM promotes malignant stem cell–like states in aggressive AMLs by directly repressing prodifferentiation gene regulatory programs.A MECOM-boun