Tineke Lenstra

A lot of thanks for the hard work and persistence of Jos Meeussen, and for the invaluable contributions of Wim Pomp, Wim de Jonge and Davide Mazza. 10/10

Overall, these findings highlight that eukaryotic TF search is highly efficient. Unlike in prokaryotes, facilitated diffusion is not strictly required. Instead, we find that cooperative IDR-driven self-interactions enable rapid target recognition in eukaryotic cells. 9/10

Moreover, in the various TF truncations, cooperativity on TF search and TF binding stability are uncoupled, indicating these are independently regulated forms of cooperativity that control TF function. 8/10

Swapping this IDR with human self-interacting IDRs (EWS or FUS) restored target search, demonstrating that cooperative search depends on IDR-mediated self-interactions, and that this mechanism is general and portable across species. 7/10

To understand which TF domain mediates these cooperative self-interactions, we created truncation mutants. We identified an intrinsically disordered region (IDR) outside of the activation domain that is essential both for stable TF binding and for effective search. 6/10

We next asked if target search could be facilitated by other TF molecules. Decreasing Gal4 protein levels increased target search time, indicating that Gal4 target search is cooperative and may involve self-interactions. In addition, cooperativity also stabilizes Gal4 on DNA. 5/10

Bacterial TF search uses facilitated diffusion (diffusion+sliding/hopping). To test this in eukaryotes, we removed binding sites (TFBS) or added a roadblock (yellow) to limit hopping/sliding. This did not increase search time, indicating facilitated diffusion is not required for this TF. 4/10

Here, we directly visualize TF search by labeling a single TF per nucleus and measuring target search to a specific endogenous locus. Using budding yeast TF Gal4, we find a search time just over 5 min, close to but not exceeding the diffusion limit, indicating search is highly efficient. 3/10

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs. How do they find these short DNA sequences within the enormous genome? This search process of eukaryotic TFs is largely unclear due to the lack of direct measurements in living cells. 2/10

Ever wondered how a eukaryotic transcription factor finds its specific DNA motif in the vast genome? In this preprint, we directly measured the dynamics of this search process in living cells, revealing a cooperative mechanism mediated by disordered regions. 1/10 doi.org/10.64898/202...

Epigenetics 2025 | Xcells Conferences

Great speaker lineup at the Epigenetics conference in Brussels, September 24-26th. There are still open slots for short presentations, register here: www.xcellsconferences.com/epigenetics2...

🚨Our call is open NOW! Join our PhD program in Amsterdam. Deadline: Feb. 28. Apply here: bit.ly/3O4bOjq #PhD

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Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics Gene promoters and enhancers share the same constrained mobilities during transcription, opposing cohesin-mediated loop extrusion.

Out now in
@ScienceAdvances
👇 science.org/doi/10.1126/... BRAVO @tomsexton_lab and super help from @tinekelenstra.bsky.social
@mitchell_lab @akispapantonis.bsky.social
@molina_lab @evisoutoglou.bsky.social @NeoVirTech

Registrations are open for the first edition of 'Gene regulation, one molecule at a time'! Very excited to bring #SingleMoleculeGenomics and #SingleMoleculeImaging community together @embl.org !
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Thanks Leila!

Thanks, congrats to you too!

Thanks Cees! And also congrats to the other awardees!

Thanks, Christa!

Congrats to you too Christa!

Immensely honored and happy to receive the ERC Consolidator Grant! Looking forward to image many more single molecules in the coming years.

Looking for a PhD position? Interested in understanding gene regulation using live-cell single-molecule imaging technologies? Apply for the NKI PhD program to join our lab or other NKI labs. bit.ly/3O4bOjq