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... 🧵

We are so excited to see our work out in @nature.com! We present a multi-omic single-cell atlas of 12 organs in human fetal development, explore the enhancer landscape, use deep learning to infer rules of transcription factor activity, and interpret non-coding variants in complex traits: #GeneReg 🧬🖥️

First first-author paper out! 🎉

We show that the classically repressive mark H3K27me3 can be linked to active transcription through a newly identified reader complex 🤯

Really grateful to everyone involved in this project during my PhD!

Thread below 👇

Our H1 paper is out #ScienceAdvances:
www.science.org/doi/10.1126/...
@masaashimazoe.bsky.social et al. reveal that linker histone H1 acts as a liquid-like glue to organize chromatin in live cells. 🎉 Fantastic collab with @rcollepardo.bsky.social @janhuemar.bsky.social and others—huge thanks! 🙌 1/

A H3K27me3 reader complex couples H3K27me3 accumulation to nascent transcription of transposable elements in Paramecium - Genome Biology Background The ability to deposit histone H3K27-trimethyl (me3) marks is essential for transcriptional repression by Polycomb Repressive Complex 2 (PRC2). This is largely attributed to Polycomb repres...

Our latest publication is now out at Genome Biology!
link.springer.com/article/10.1...

We uncover a unique association between a H3K27me3 reader complex and active transcription.
A thread with our key findings: (1/8)

#TEsky #Polycomb #transcription #smallRNAs

ChromSMF preprint is out!🚀
tinyurl.com/ChromSMF

We often piece together chromatin regulation layer by layer from separate assays. But this can be limiting!

In @arnaudkr.bsky.social's lab, we developed a method to directly study multiple layers on the same DNA molecule! 🧬

What does this unlock? ⬇️

Delighted to see our work now published at the EMBO Journal! Check also this concomitant paper by the Bai and Mirny labs with an orthogonal approach that aligns well with our measurements www.nature.com/articles/s41... Great system to study how SMCs facilitate/regulate target search in chromatin!

🧵 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...

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...

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...

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
⬇️
www.biorxiv.org/content/10.6...
⬆️

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)