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Hanneke Vlaming

@hannekevlaming.bsky.social

Assistant Prof at Utrecht University, studying the process of transcription elongation vs early termination. (she/her)

18 Posts323 Follower170 Folgt
Surfin' NuRD@surfinnurd.bsky.social · 6mo ago

OK Kids, our ERK story is finally heading out into the world. After 9 years of having funding, losing funding, losing staff, getting funding, gaining staff...it's ready! We discovered a novel stage of what is an otherwise extensively studied process: how cells respond to extracellular signals. 1/n

biorxiv.org

Elzo de Wit lab @ NKI@dewitlab.bsky.social · 7mo ago

🧵 CTCF is essential for embryonic development, but why has remained unclear. By combining gastruloids with a temporal degron system, we uncovered a surprising dual function — and it changes how we think about CTCF's role in development. 1/8 www.biorxiv.org/content/10.6...

A dual role for CTCF in development

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

biorxiv.org

Hanneke Vlaming@hannekevlaming.bsky.social · last yr.

Thrilled to be one of the ERC StG awardees this year! It will allow my team to further delve into the puzzle of what regulates the fate of RNA Polymerase II during early elongation: will it terminate early, or elongate happily ever after?

European Research Council (ERC)@erc.europa.eu · last yr.

📣 The ERC Starting Grant call results are out! Find out which early-career researchers will receive funding this year, what they will be investigating, where they will be based... plus lots of other #ERCStG facts & figures for 2025! ➡️ buff.ly/IsafuFh #FrontierResearch 🇪🇺#EUfunded #HorizonEurope

Suyang Zhang@suyangzhang.bsky.social · last yr.

A transcription balance required for genome stability 🧬⚖️ Our work on RNA Pol II transcription speed control by the DNA helicase RECQL5 and the transcription-coupled DNA repair complex is now on @natsmb.nature.com #CryoEM #transcription #genomestability www.nature.com/articles/s41...

Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation - Nature Structural & Molecular Biology

Using cryo-electron microscopy and biochemistry, Zhang et al. reveal that the DNA helicase RECQL5 and the transcription-coupled DNA repair complex coordinate to regulate transcription elongation rates...

nature.com

Hanneke Vlaming@hannekevlaming.bsky.social · last yr.

Happy to share this paper! We uncovered that good 5' splice sites protect against ZC3H4/Restrictor's promiscuous role, and that its role is to suppress elongation and indirectly cause termination. Looking forward to learning more about this protein in the future!

Genes & Development@genesdev.bsky.social · last yr.

In this study, Mimoso et al. show that Restrictor serves as a transcriptional safeguard that suppresses the spurious transcription of non-coding RNAs, while preserving mRNA transcription. Learn more here: ➡️ tinyurl.com/gd352654