Simon Gaudin

Incredibly proud to share our new preprint, lead by the Incomparable Rithika Sankar.
Here we temporally dissect the role of FACT in mES cells, finding that FACT loss drives progressive deterioration of chromatin architecture, leading to transcriptional collapse.
www.biorxiv.org/content/10.6...

Excited to share this work done during my PhD here in Vienna!

We show how chromatin compaction prevents the release of fragmented DNA in apoptosis, and use new tools to study the mechanism of compaction itself.

See our summary/"bluetorial" below & our preprint here: www.biorxiv.org/content/10.6...

Our work on the interplay between loop extrusion and chromatin mechanics is finally out in @physrevresearch.bsky.social . Congrats @hosseinsalari.bsky.social for the hard work ! 👏
journals.aps.org/prresearch/a...

New paper alert from the group!! 🚨: DNA flexibility tips the balance between stability and plasticity in nucleosomes

One of the works from my PhD, co-led alongside @nachper.bsky.social, is finally out! Work from @rcollepardo.bsky.social & @janhuemar.bsky.social
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www.biorxiv.org/content/10.6...
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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:

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 🧵👇

🧪🧬New preprint We present cryo-EM structures of reconstituted CTCF–nucleosome complexes, showing CTCF dimerization drives nucleosome oligomerization into defined higher-order assemblies. Disrupting CTCF–CTCF interfaces in mESCs reduces looping and impairs differentiation. tinyurl.com/CTCF-nucleos...

SS18::SSX activates Polycomb target genes without BAF ❌
Instead, transcription relies on EP300 via the SS18 QPGY domain
www.biorxiv.org/content/10.6...
➡️ Coactivator targeting emerges as a new therapeutic strategy in synovial sarcoma 🎯
Team work from @banitolab.bsky.social and @uoe-igc.bsky.social

Have you wondered how the rules of chromatin folding have evolved? Well, this task is not easy to formalize. But here is our take on it: train species-specific DNA-to-chromatin encoder, apply to DNA of unseen species, and build chromatin rules-based tree of life. Have a look:
doi.org/10.1093/nar/...

Dissecting gene regulatory networks governing human cortical cell fate - Nature Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissecti...

1/ Our new study, led by Jingwen Ding, examines the role of transcription factors during human neurogenesis to identify gene regulatory networks influencing cell fate, maturation, and subtype specification
www.nature.com/articles/s41...

Preprint alert: Jiangyuan Liu developed a new workflow for chromatin loop calling across Hi-C datasets, e.g., during differentiation. Most loops are shared between datasets/cell states. Important work for all interested in chromatin loops and how to identify them!

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

Antisense transcription can induce expression memory via stable promoter repression - Genome Biology Background The capacity of cells to retain a memory of previous signals enables acquisition of unique fates and adaptation to their environment. The underlying gene expression memory can arise from mu...

⚠️ The final work of two former PhD students Till @tschwammle.bsky.social and Verena @verenamutzel.bsky.social is out!
➡️⬅️ They dissect how memory can arise from antisense transcription using mathematical modelling 💻, genomics 🧬 and synthetic biology ⚒️! link.springer.com/article/10.1...

H4K16 acylations destabilize chromatin architecture and facilitate transcriptional response during metabolic perturbations Nitsch et al. show that short-chain acylations of histone H4K16, acetylation (C2), propionylation (C3), and butyrylation (C4) modulate chromatin structure in vitro. These effects can translate in vivo...

Now final version out: Our manuscript connecting histone modifications with metabolism: How H4K16 acylations regulate inter +intranucleosomal interactions and confer resilience to metabolic challenges in vivo. Thanks to the team+ @sandrani.bsky.social

Enjoy 👇👇 www.cell.com/molecular-ce...

Our work on #RegulatoryTrajectories is out today in Nat. Comms: www.nature.com/articles/s41...
Led by @raquelrouco.bsky.social, this study establishes a new framework to study how enhancer landscapes act sequentially at developmental loci and are silenced to shape gene expression patterns. (1/n)

High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivo TFIID is instrumental in recognizing promoter sequences and initiating transcription, yet a cohesive understanding of how this complex interacts with and functions at different promoter types in vivo ...

The @zeitlingerlab.bsky.social is pleased to announce @sergio-gma91.bsky.social’s preprint “High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivo” (www.biorxiv.org/content/10.6...).

TLDR; TFIID behaves differently depending on promoter type. More below:

The transcription of a single olfactory receptor per neuron is enforced by epigenetic silencing of their enhancers The ability to discriminate thousands of odors in our environment requires each olfactory neuron to express a single olfactory receptor from hundreds of available genes. The biochemical mechanism enfo...

This went under the radar but answers a fundamental question in Epigenetics...

From many hundreds of olfactory receptor genes, each neuron selects expression of only single one (near-randomly). How?

Outstanding work from Mathieu Boulard and colleagues

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

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm Nature Cell Biology - Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through...

Happy to share that my postdoc work with @jobdekker.bsky.social is out!
rdcu.be/eWHD2

We characterize interphase chromatin folding programs with distinct modes of mitotic inheritance and identify the chromosome-intrinsic capacity to form a microcompartment of active CREs during mitotic exit.

Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️
Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬

RNA polymerase II initiation factors show different dynamic behaviour upon induced transcription in live cells Transcription by RNA polymerase II (Pol II) requires the ordered action of general transcription factors (GTFs) forming the pre-initiation complex (PIC). How these events unfold kinetically remains un...

Read our new preprint where we uncover a hierarchy in human PIC assembly and establish a quantitative framework that connects factor exchange kinetics to the regulation of Pol II activity in living human cells. doi: doi.org/10.64898/202...
By A. Oravecz and our collaborators @molinalab.bsky.social

Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo Enhancers control tissue-specific gene expression across metazoans. Although deep learning has enabled enhancer prediction and design in mammalian cell lines and invertebrate systems, it remains uncle...

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: www.biorxiv.org/content/10.6... . Amazing collaboration by @shenzhichen1999.bsky.social, Vincent Loubiere (@impvienna.bsky.social,@viennabiocenter.bsky.social),... (1/2)

🚨Our work on the impact of DNA replication on 3D genome is out in Genome Biology: replication-dependent loop extrusion by sister-forks, wave of replication, no evidence for large-scale replication factory. Great collab with @aurelepiazza.bsky.social. More here: link.springer.com/article/10.1...

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm - Nature Cell Biology Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

Exciting new paper out! @allanaschooley.bsky.social and Sergey Venev led this project that let to the discovery of two chromosome folding programs: one inherited via mitotic chromosomes and one mitotic inherited through the cytoplasm!

www.nature.com/articles/s41...

Took us a bit, but proud of this published version. We now examine the genetic interaction of phosphorylation with oligomerization and where bulk and phospho-Swi6 localize. Wonder if chromatin affinity tuning to enable Suv39 H3K9me3 spreading is a conserved mechanism ?

doi.org/10.1093/nar/...

🚨New paper out! In our @MolCellNews paper, we solve a piece of the puzzle of how our genome folds. We found the two specific molecular "brakes" in the CTCF protein that stop DNA loop extrusion. One of the final pieces of my PhD!
tinyurl.com/29uuc5by

Cohesin guides homology search during DNA repair using loops and sister chromatid linkages Accurate repair of DNA double-strand breaks (DSBs) is essential for genome stability, and defective repair underlies diseases such as cancer. Homologous recombination uses an intact homologous sequenc...

I am happy to share that my postdoctoral work in the @gerlichlab.bsky.social at @imbavienna.bsky.social is finally out 🎉!
Our study reveals how cohesin guides focused and accurate homology search.
Read more 👉 www.science.org/doi/10.1126/...
Follow along for key insights and updates! 🧵

📣 I hereby make my Bluesky debut to announce that our work linking DNA binding affinities and kinetics 𝘪𝘯 𝘷𝘪𝘵𝘳𝘰 and 𝘪𝘯 𝘷𝘪𝘷𝘰 for the human transcription factor KLF1 just got published in Cell! @cp-cell.bsky.social

www.cell.com/cell/fulltex...

Key findings in a thread (1/6):

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/...

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The SMC Hinge is a Selective Gate for Obstacle Bypass - Nature Communications SMC complexes are ring-shaped motors that fold DNA by extruding loops, but how they navigate large DNA obstacles is unclear. Here, Liu et al., show that SMC complexes bypass obstacles by threading obs...

The hinge bypass gate paper is finally out! doi.org/10.1038/s414...

We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.

A lucky convergence of 3 projects lead to the initial discovery!

Intracellular competition shapes plasmid population dynamics From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...

Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...

Gene-scale in vitro reconstitution reveals histone acetylation directly controls chromatin architecture Reconstituting 20-kb chromatin shows that tuning acetylation alone reshapes its folding, dynamics, and contact domain formation.

To probe gene-scale chromatin physics, we built 96-mer (20 kb) arrays with defined histone marks. Combining single-molecule tracking, AFM imaging, and developing in vitro Hi-C, we saw how specific modifications dictate chromatin structure and dynamics. www.science.org/doi/10.1126/...