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Posts by Pia Mach

Cohesin-mediated loop extrusion and enhancer-associated factors additively contribute to Sox2 looping with its distal enhancer A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields

New paper in Genes & Dev: we dissected how Sox2 — a key pluripotency TF — is regulated by a distal enhancer cluster (SCR) 100 kb away. The results challenge simple models of cohesin-mediated loop extrusion of gene regulation. genesdev.cshlp.org/content/earl... 🧵

6 days ago 48 21 2 1

Want to know how histone marks regulate your favorite gene? Go single molecule with ChromSMF: integrated measure of chromatin accessibility and histone marks + DNA methylation, TF footprints and genotype for free! Very proud of @mpalamin.bsky.social ! @embl.org

4 weeks ago 70 17 1 0

🔥 How does CTCF shape enhancer–promoter communication?

In our new preprint, we systematically test how the position and orientation of CTCF binding sites (CBSs) influence gene regulation at the mouse Sox2 locus.

🧪 full paper can be found here: www.biorxiv.org/content/10.6...

4 weeks ago 26 12 1 1

New preprint from our lab... We applied our hopping technology to relocate CTCF binding sites to thousands of alternative positions in the Sox2 locus: www.biorxiv.org/content/10.6...

1 month ago 42 17 0 0
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

🧵 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...

1 month ago 112 55 7 4
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How do pairs of DNA loci - such as enhancers and promoters - find each other inside the nucleus? 🤔

Most models assume the random forces driving locus motion are independent in space

New preprint by
@janniharju.bsky.social: this assumption fails in living cells 🧵

www.biorxiv.org/content/10.6...

1 month ago 113 46 3 1

Tomorrow I’ll be presenting at the 2026 CSHL Systems Biology meeting! 🧬

Join to hear about ChromSMF, a genomic method for integrated measurement of histone modifications, protein-DNA interactions, and DNA methylation on the same multi-kilobase DNA molecules! 🚀

Preprint coming soon 😉

1 month ago 30 3 0 2

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...

1 month ago 95 40 1 2
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Acute NIPBL depletion reveals in vivo dynamics of loop extrusion and its role in transcription activation - Nature Genetics Acute depletion of NIPBL reveals a class of chromatin loops that are independent of NIPBL for their maintenance but not their establishment and that NIPBL is necessary for the expression of lineage-de...

Very excited to share my postdoc research in the @jesserdixon.bsky.social lab at @salkinstitute.bsky.social, out online at @natgenet.nature.com today! www.nature.com/articles/s41... We investigated the function of the cohesin accessory protein NIPBL, making two particularly interesting findings:

2 months ago 37 24 1 1
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Interested in transcriptional regulation, enhancers and 3D genome folding?

In this new study we wondered about the role of cohesin loading at enhancers for long-range transcriptional control

www.biorxiv.org/content/10.6...

detailed 🧵👇

2 months ago 67 33 1 3
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Happy to share part of my postdoctoral work at the @lucas.farnunglab.com lab. Great collaboration with @voslab.org and @andersshansen.bsky.social. “Structural basis for CTCF-mediated chromatin organization” www.biorxiv.org/content/10.6...

2 months ago 30 10 0 0

Very excited to share our new paper 🎊
A wonderful early birthday gift! 🎂🎁
Huge thanks to everyone who contributed to making this possible.

4 months ago 5 1 0 0

Here is a copy of last year's Twitter thread explaining our preprint - jump to (21) for the new stuff 👀

Synergy between cis-regulatory elements can render cohesin dispensable for distal enhancer function

now revised and journal accepted at www.science.org/doi/10.1126/...

🧵👇

4 months ago 90 45 4 3
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📣 Paper alert!

I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...

5 months ago 123 49 7 6
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How can we organize current theoretical approaches for developmental biology - from information to dynamical systems & GRNs - into a common framework?

We propose to think along Marr's 3 levels: computational problem, algorithm, implementation

Check out our review:
arxiv.org/abs/2510.24536

5 months ago 49 13 1 2
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🥁This Wednesday , in #FragileNucleosome seminar, we are excited to host @hannahlong.bsky.social and @jeffvierstra.bsky.social to tell us about amazing work they are doing!
🗓️Register here for upcoming session and the entire series:
us06web.zoom.us/webinar/regi...

5 months ago 20 12 0 0
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Characterization of induced cohesin loop extrusion trajectories in living cells Nature Genetics - This study introduces a system called TArgeted Cohesin Loader (TACL) that recruits cohesin complexes at defined genomic regions and induces loop extrusion events in living cells,...

The TArgeted Cohesin Loader (TACL) paper was just published. Happy that we were able to contribute to this really exciting project!

If you want to learn how targeting cohesin to defined loci in the genome affects the local chromatin environment and transcription, look no further!

rdcu.be/eLiT5

6 months ago 54 20 0 0
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Happy to share our latest publication, in which we show that the arrangement of nucleosomes around CTCF sites contributes to higher-order organisation of chromatin into TADs: www.embopress.org/doi/full/10....

5 months ago 71 31 0 2
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Out now! 🎉 Check the thread & preprint to see why we think E–P specificity is real in mammals — and, well, a few other interesting things popped up too 👀
Huge thanks to @danielibrahim.bsky.social, @arnaudkr.bsky.social & @stemundi.bsky.social and fantastic people in their labs — what a journey! 🧪🔬

6 months ago 44 13 1 0
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Enhancer-promoter compatibility is mediated by the promoter-proximal region Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...

What is a promoter? And how does it work?

We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters

www.biorxiv.org/content/10.1...

6 months ago 173 74 2 6
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Functional maps of a genomic locus reveal confinement of an enhancer by its target gene Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt...

Our reporter hopping scaled up to thousands of integrations in a single locus, to produce high-resolution functional maps, with plenty of interesting insights: www.science.org/doi/10.1126/...

6 months ago 34 11 0 0

Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇

6 months ago 115 52 8 5

Have you ever wondered how the exact location of a gene affects it's activity?

The main story of my PhD deals with exactly that question, and is now published in Science! ✨
www.science.org/doi/10.1126/...

My amazing co-author and friend @mathiaseder.bsky.social summarized the highlights for you

7 months ago 36 13 1 2
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Functional maps of a genomic locus reveal confinement of an enhancer by its target gene Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt...

✨Exciting news: the main story of my PhD is out in Science!

Together with Christine Moene @cmoene.bsky.social, we explored what happens when you scramble the genome—revealing how Sox2’s position shapes enhancer activation.

📖 Read the full story here: www.science.org/doi/10.1126/...

7 months ago 95 37 3 1

Very proud of our paper on "scrambling-by-hopping" LADs, which was just published: www.nature.com/articles/s41.... Congrats to Lise Dauban and the rest of the team – this was a real tour-de-force!

7 months ago 58 24 0 0

This is not a HiC map! Ever wondered if multiple enhancers get activated simultaneously? We measured chromatin accessibility on thousands of molecules by nanopore to create genome-wide co-accessibility maps. Proud of @mathias-boulanger.bsky.social @kasitc.bsky.social Biology in the thread👇

8 months ago 113 34 10 0
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NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

www.biorxiv.org/content/10.1...

8 months ago 117 54 1 6
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Synthetic engineering demonstrates that synergy among enhancers involves an increase in transcriptionally productive enhancer-gene contacts Enhancers are non-coding cis-regulatory elements that control the expression of distally located genes in a tissue- and time-specific manner. Recent studies indicate that enhancers can differ in their...

Excited to share the latest work from the lab led by @eharo84.bsky.social, in which we have used synthetic biology to explore the mechanisms by which different types of long-range enhancers ensure robust and precise developmental gene expression

www.biorxiv.org/content/10.1...

8 months ago 66 37 5 2
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We found a new asymmetry in the large-scale chromosome structure: sister chromatids are systematically shifted by hundreds of kb in the 5′→3′ direction of their inherited strands! The work was led by Flavia Corsi, in close collaboration with the Daniel Gerlich lab.
www.biorxiv.org/content/10.1...
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9 months ago 115 59 3 7

Calling all aspiring Postdocs! One extra week to apply to join our exciting HFSP-funded project to uncover how chromatin moves to function.

Deadline July 15th.

www.mdc-berlin.de/career/jobs/...

9 months ago 15 16 0 0