Michal Gdula

Are you a DNMT3 enthusiast wondering how they achieve specificity at CpG islands during development? And why is DNMT3B specifically required for methylation on the inactive X?

We set out to dissect the mechanism, now published in Genes & Development
genesdev.cshlp.org/content/earl...
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Tread -1- EpiSci - I am very proud to share with you our new study that you can access on @biorxivpreprint.bsky.social (see link below)
"The Interaction with Nanotopographical Environment regulates nuclear mechanoresponse in mESCs via Histone Demethylase KDM3A.
www.biorxiv.org/content/10.6...

FDA won’t review Moderna application for first mRNA-based flu vaccine The decision, which shocked company officials, comes as the FDA says it will take a stricter approach to federal vaccine approvals.

So the feds ARE NOT considering an mRNA vaccine for the flu, which could save countless lives, but ARE backing research into whether horse dewormer can cure cancer, because the right views vaccines as elite and ivermectin as populist.

Cool.
kffhealthnews.org/news/article...

We’re recruiting! Three-year, fully funded #postdoc opportunity: pancreatic cancer #epigenetics & potential new treatments (funded by @ncn.gov.pl & @dfg.de ). Collaboration with @akispapantonis.bsky.social, University of Göttingen (OPUS-LAP). See the ad & contact me! drive.google.com/file/d/1vrFd...

Check out our new findings showing BRD4's role in preventing the premature activation of developmental transcription factors via #Polycomb, providing new mechanistic insights into the pathogenesis of neurodevelopmental disorder #CdLS #NDDs, #chromatinopathies www.biorxiv.org/content/10.6...

This Friday @uam-ibmib.bsky.social seminar: Maja Szymańska-Lejman @szymanskalejman.bsky.social will tell us about reprogramming meiotic #recombination with dCas9 - Don't miss it! #meiosis

Chromatin Loop prediction via Accessibility Model for Protein-mediated loops

github: github.com/chikit2077/...

What drives CGG RAN translation in #FXTAS? Anna Baud & Krzysztof Sobczak with Rajani Gudipatti & Malgorzata Borowiak all from @uam-ibmib.bsky.social just published at Nature Communications : IGF2BP3 regulates FMRpolyG—promising FXTAS target. www.nature.com/articles/s41...

Deep-learning prediction of gene expression from personal genomes link.springer.com/article/10....

Fig. 1: Schematic of the human telomeric chromatin architecture. The human telomere is made up of TTAGGG repeats arranged into nucleosomes, bound by a six-subunit shelterin complex (comprising TRF1, TRF2, RAP1, TIN2, TPP1 and POT1). Some complexes are depicted without TPP1 and POT1, which it has been suggested are less abundant than the other subunits. Recent in vitro structural analyses of telomeric chromatin revealed a columnar stacking of histones on TTAGGG repeats, characterized by face-to-face nucleosome arrangements, as well as an alternative open configuration where two histone octamers are oriented at a nearly 90° angle. These in vitro columnar arrays exhibit an NRL of approximately 130 bp. In vivo, however, the telomeric NRL is 157 bp, longer than the NRL of the proposed columnar histone arrangement, but shorter than the ~197-bp NRL of bulk chromatin. To reconcile this, we depict here a model in which shelterin remodels the telomeric chromatin to integrate features of a columnar nucleosome organization with the nucleosome periodicity observed in vivo. At the telomere terminus, a 3′ single-stranded overhang of TTAGGG repeats invades the duplex telomeric DNA to form a lariat structure known as the T-loop. This loop structure serves a protective function by preventing the telomere from being recognized as damaged DNA. The size of the T-loop is variable and may differ between telomeres, contributing to the structural heterogeneity of the telomere. The extent to which nucleosomes are present within the T-loop remains unclear.

Fig. 2: Impact of the TPE on the local and distal chromatin environment. Telomere elongation results in the repression of genes in the vicinity of telomeres, a phenomenon known as the TPE. a, Schematic of the repression of telomere-proximal genes via the classical TPE that has been shown at telomere-adjacent artificial reporter genes in human cells. Upon elongation, telomeres accumulate repressive histone modifications (indicated in red) through the activity of a histone methyltransferase (HMT) and HP1. The repressive heterochromatin environment of elongated telomeres spreads to nearby subtelomeric genes (indicated with red and orange DNA strands), resulting in transcriptional repression. The strength of silencing diminishes as the distance from the telomere increases (indicated with fading arrows). Conversely, upon telomere shortening, the human TPE (at telomere-adjacent transgenes) is characterized by loss of the repressive histone modification H3K9me3 and gain of the activating modification H3K9ac. In contrast to telomere-adjacent artificial reporter genes, at natural subtelomeres, spreading of repressive histone modifications from telomeres is not consistently observed, probably due to the presence of boundary elements. b, Schematic of telomere-mediated repression of telomere-distal genes via TPE-OLD. Elongated telomeres acquire the ability to form long-distance loops between telomeres and interstitial telomere sequences (ITSs; that is, sequences of TTAGGG repeats outside of the telomeres). Looping requires binding of shelterin to an ITS and results in transcriptional repression of the affected gene.

Fig. 3: Heterogeneity of (sub)telomeric chromatin and its reorganization upon telomere elongation. a, Telomeric and subtelomeric chromatin are organized into distinct domains. The subtelomeric TAR1 site acts as a TSS for the telomeric non-coding RNA TERRA (depicted in red for UUAGGG and in orange for subtelomere-derived RNA). The canonical TERRA promoter contains a high density of CpG dinucleotides, regulated by the DNA methyltransferases DNMT1 and DNMT3B. In contrast, certain subtelomeres (variable across cell lines) contain non-canonical TERRA promoters that lack CpG-rich regions and escape regulation by DNA methylation. Binding of CTCF and cohesin to the centromeric side of TAR1 maintains transcriptionally competent chromatin at the TSS and facilitates the recruitment of RNA polymerase II. The telomeric tract itself displays a bivalent pattern of histone modifications, with both activating (H3K4me3 and H3K27ac) and repressive marks (H3K9me3, H3K27me3 and H4K20me3). TERRA modulates this environment through the formation of RNA:DNA hybrids (R-loops) and G4s. Furthermore, RNA- or G4-binding chromatin remodellers, including Suv39H1, ORC1, NoRC, PRC2 and FUS, are recruited by TERRA and alter the epigenetic landscape. G4-binding proteins, including CTCF and YY1, mediate long-range interactions between distal G4s, contributing to higher-order chromatin organization. The telomeric shelterin complex itself is heterogeneous and probably assembles into subcomplexes (for example, TRF1–TIN2–TPP1–POT1 or TRF2–RAP1). TRF2 is essential for formation of the terminal T-loop, which requires direct interaction between TRF2 and nucleosomes. TRF2-mediated stabilization of nucleosomes may prevent branch migration at the base of the loop, which would result in cleavage of the loop by resolvases. b, TERT-mediated elongation alters the chromatin of telomeres. The length of TERRA molecules is proportional to the telomere length, allowing increased recruitment of chromatin-modifying enzymes…

Fig. 4: Schematic of the ALT pathway. ALT is a telomerase-independent, cancer-specific mechanism of telomere maintenance enabled by alterations to the telomeric chromatin. Between 10 and 15% of cancers activate the ALT pathway to maintain telomere length in a telomerase-independent manner. ALT+ cancers frequently display loss of ATRX–DAXX histone chaperone activity, resulting in reduced deposition of the histone variant H3.3 at telomeres and, consequentially, progressive decompaction of the telomeres. This chromatin disruption promotes increased TERRA transcription, leading to accumulation of R-loops and G4s. ALT+ telomeres also display increased levels of the repressive histone mark H3K9me3, partially due to additional mutations such as those encoding the G34R substitution in H3.3 and the R132H substitution in IDH1, which inhibit the histone demethylase KDM4B. The combined effect of R-loops, G4s and decreased nucleosome occupancy cause persistent replication stress, ultimately giving rise to telomeric breaks. Broken telomeres are further enriched in H3K9me3 due to the break-induced recruitment of the CHAMP1–POGZ–HP1 complex. These telomeric breaks are clustered in APBs, membrane-less condensates formed through HP1- and PML-dependent phase separation. Within APBs, broken telomeres invade homologous telomeric templates to initiate HDR-mediated extension. Invasion of the broken strand is stimulated by RAD51AP1, which promotes the switch from TERRA R-loops to stable telomeric D-loops, where telomere elongation takes place.

Structural organization and function of telomeric chromatin [Review by Ruben van der Lugt & Jacqueline Jacobs] www.nature.com/articles/s41...

Postdocs at Center for Gene Expression in Department of Cellular and Molecular Medicine - Copenhagen, Hovedstaden (DK) job with University of Copenhagen | 12849488 We are looking for 2 or more highly motivated postdocs interested in ribosome biology, 3D chromatin organisation, or regulation of protein turnove...

We are looking for a Postdoc at the Center for Gene Expression in Copenhagen. Deadline for applications is the 11th of January. If you are interested in 3D chromatin, SMC complexes, and super-resolution microscopy, join us. www.nature.com/naturecareer...

In the most recent episode of the Epigenetics Podcast, we talked with Mitch Guttman from Caltec about ChIP-DIP (Done In Parallel). #podcast #epigenetics

Listen here: activemotif.com/podcasts-mit...

Region Capture Micro-C and 3D Genome Structure (Anders Sejr Hansen)

Excellent @activemotifusa.bsky.social epigenetics podcast w @andersshansen.bsky.social

It’s interesting, while going through specific projects and lines of questioning, the conversation acts as a nice reflection of the state of our field (fields?)

Lots of ideas!

open.spotify.com/episode/19Nd...

Multistep genomics on single cells and live cultures in subnanoliter capsules Single-cell sequencing methods uncover natural and induced variation between cells. Many functional genomic methods, however, require multiple steps that cannot yet be scaled to high throughput, inclu...

@science.org Multistep genomics on single cells and live cultures in subnanoliter capsules | Science www.science.org/doi/10.1126/...

Chromatin buffers torsional stress during transcription During eukaryotic transcription, Pol II must overcome nucleosome obstacles and, because of DNA’s helical structure, must also rotate relative to DNA, generating torsional stress. However, there is lim...

@science.org Chromatin buffers torsional stress during transcription | Science www.science.org/doi/10.1126/...

Escape from X inactivation is directly modulated by Xist noncoding RNA Nature Cell Biology - The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape...

Very happy to share our paper rdcu.be/eUImj out today in @natcellbio.nature.com 🎉🎉🎉
We uncover an unexpected role for endogenous Xist RNA in regulating X-linked genes that escape X-inactivation.

Can't believe it's that time of year - registration already open for next year's Transcription & Chromatin meeting. Almost half the talks are selected from the abstracts, so register soon before it fills up. This is a very lively meeting, with plenty of time to discuss over dinner & at the bar

SET1/MLL complexes control transcription independently of H3K4me3 Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...

An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost!

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

Generative epigenetic landscapes map the topology and topography of cell fates | PNAS Epigenetic landscapes were proposed by Waddington as the central concept to describe cell fate dynamics in a locally low-dimensional space. In mode...

Very happy to share our 'Evoscape' paper, now published in PNAS ! www.pnas.org/doi/10.1073/...

so many grand gestures welcoming US researchers - neglecting the fact that funding in Canada, Australia, Europe and China is already fiercly competitive. This is not the solution. #standupforscience

Summary - Summer School on Chromatin Biology: A Hands-On Expedition

👉 Chromatin Summer School 2026 – Apply Now!
Join us in Munich 17–29 August 2026 for an immersive program on chromatin biology:
🔬 Expert lectures
🧪 Hands-on training
🤝 Global networking
Open to 14 PhD students worldwide (sponsorship available)
👉 Apply here: bit.ly/4oGDR8f
#ChromatinBiology

Confused by all the histones that are cropping up in organisms that are decidedly NOT eukaryotes? check out our review - fantastic work by team NucEvo in the #Lugerlab
The Expanding Histone Universe: Histone-Based DNA Organization in Noneukaryotic Organisms - www.annualreviews.org/content/jour...

A vision of chromosome organization Cryogenic electron tomography of condensed chromatin enables multiscale analysis of its structure

@science.org 🧬🔬 A vision of #chromosome organization | Science www.science.org/doi/10.1126/...
@vram142.bsky.social et al.

Multiscale structure of chromatin condensates explains phase separation and material properties The structure and interaction networks of molecules within biomolecular condensates are poorly understood. Using cryo–electron tomography and molecular dynamics simulations, we elucidated the structur...

@science.org 🧬🔬 Multiscale structure of #chromatin condensates explains phase separation and material properties | Science www.science.org/doi/10.1126/... @janhuemar.bsky.social et al.

Join us this Friday morning for the @uam-ibmib.bsky.social seminar: Józef Dulak from the Jagiellonian University @jagiellonskiuni.bsky.social will give a talk on the modeling cardiac and muscle diseases with induced pluripotent stem cells! #IPSCs

Great news for @uam-ibmib.bsky.social! Three @ncn.gov.pl OPUS grants to our researchers: @juliadluzewska.bsky.social, Wojciech Szlachcic and a collaborative Polish-German OPUS-LAP grant to @michal-gdula.bsky.social & @akispapantonis.bsky.social from @uni-goettingen.de. Big congrats to everyone!

Did you know that changes in pre-mRNA 3' cleavage and RNAPII termination can go in different directions? Even more, the spacing between these two events is linked to the gene expression level❗️Check out our latest pre-print to learn more tiny.cc/330w001 1/6

Join us this Friday morning for the @uam-ibmib.bsky.social seminar: Agata Starosta @agatastarosta.bsky.social from the Institute of Biochemistry and Biophysics PAS will give a talk on on translational control in #BacillusSubtilis during sporulation! #translation

Conrad Hal Waddington was born OTD in 1905.

His “epigenetic landscape” is a diagrammatic representation of the constraints influencing embryonic development.

On his 50th birthday, his colleagues gave him a pinball machine on the model of the epigenetic landscape.

🧪 🦫🦋 🌱🐋 #HistSTM #philsci #evobio

Join us on Friday for @uam-ibmib.bsky.social IBMiB seminar of Halina Petrykowska from our Department of Gene Expression to learn about male-specific #miRNAs whihc regulate sperm development and function in Marchantia polymorpha!