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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...

We are looking for PhD student in the group of Dr. Francesca Mattiroli at the Hubrecht Institute. The successful candidate will work in a collaborative project between the Mattiroli lab and the lab of...

Join our team to contribute to the operation and innovation of state-of-the-art cryo-electron microscopes and empower groundbreaking research.

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

In this study, an imaging technology, “VISUN,” is developed that allows live-cell visualization of unmodified influenza virus during infection with single-vRNP resolution. Combining VISUN with multipl...

06-07 July 2026 | Munich, GermanyDNA Replication and Its Impact on Genome and Chromatin MaintenanceWe are RepliFate, a European Training Doctoral Network dedicated to understanding how DNA replication...

Nature - PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Protein degradation by the proteasome is central to cellular homeostasis and has been studied extensively using biochemical and structural studies. Despite an in-depth understanding of core proteolytic activity, it has remained largely unresolved how individual proteasomes process substrates inside living cells where many substrate types and co-factors exist. Here, we establish a live-cell single-molecule imaging approach that enables direct visualization and quantification of protein degradation by individual proteasomes. Using this approach, we find that substrate identity, folding and protein-protein interaction have a surprisingly modest impact on processing efficiency, whereas the mode of substrate engagement greatly impacts substrate processing; degradation initiated from protein termini typically proceeds rapidly and with high processivity, whereas internal engagement constitutes a distinct processing mode that exhibits poor processivity and a specific requirement for the AAA+ family ATPase p97/VCP. Furthermore, degradation initiated from opposite termini proceeds with asymmetric rates in a sequence-dependent manner, demonstrating that directionality is an important feature of proteasomal processing in vivo. Notably, poly-glutamine substrates associated with neurodegenerative disease are efficiently degraded from one terminus but resist degradation when engaged from the opposite terminus, highlighting the importance of substrate engagement mode. Together, our results show that different modes of substrate engagement lead to different proteasomal processing outcomes in vivo and revise the prevailing view of the proteasome as a uniform degradation machine. ### Competing Interest Statement The authors have declared no competing interest.

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Conformational biasing (CB) is a rapid and streamlined computational method that uses contrastive scoring by inverse folding models to predict protein variants biased toward desired conformational sta...

The structure and interaction networks of molecules within biomolecular condensates are poorly understood. Using cryo–electron tomography and molecular dynamics simulations, we elucidated the structur...

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