The Groth lab

tinyurl.comMaintenance of nucleosome organization through replication and transcription counteracts aberrant coalescence of active chromatinNucleosomes with their associated modifications organize and regulate the genome. It is unclear how this is integrated with the requirement of replica…

‼️🚨Out now in Molecular Cell - Our latest study 𝐫𝐞𝐯𝐞𝐚𝐥𝐢𝐧𝐠 𝐧𝐞𝐰 𝐢𝐧𝐬𝐢𝐠𝐡𝐭𝐬 𝐢𝐧𝐭𝐨 𝐅𝐀𝐂𝐓 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐢𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐜𝐞 𝐨𝐟 𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐨𝐦𝐞 𝐨𝐫𝐠𝐚𝐧𝐢𝐬𝐚𝐭𝐢𝐨𝐧 𝐟𝐨𝐫 𝟑𝐝 𝐠𝐞𝐧𝐨𝐦𝐞 𝐦𝐚𝐢𝐧𝐭𝐞𝐧𝐚𝐧𝐜𝐞: tinyurl.com/2xctvx38. It was a pleasure to lead this collaborative effort alongside @nilskrietenstein.bsky.social More in🧵below 🪡

6/7 Using machine-learning and our single-molecule data, we found nucleosome depletion and irregular, long nucleosome spacing underly AMC-forming genes. Preventing new histone deposition by CAF-1 also causes AMC formation ➡️ thus, 𝐧𝐮𝐜𝐥𝐞𝐨𝐬𝐨𝐦𝐞 𝐨𝐫𝐠𝐚𝐧𝐢𝐳𝐚𝐭𝐢𝐨𝐧 𝐜𝐚𝐧 𝐝𝐲𝐧𝐚𝐦𝐢𝐜𝐚𝐥𝐥𝐲 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐞 𝐠𝐞𝐧𝐨𝐦𝐞 𝐚𝐫𝐜𝐡𝐢𝐭𝐞𝐜𝐭𝐮𝐫𝐞 🧬

7/7 Overall, we envision that well-ordered gene body chromatin structure maintains their spatial segregation from nearby genes. 🧬 ↔️ 🧬 Great to see this #EpiC team effort finally published! With congrats to lead authors👨‍🔬@ciaranfrater.bsky.social🧑‍🔬@quimollo.bsky.social &👩‍🔬Rikke Rejnholdt Jensen🎉

4/7 Without FACT histone recycling, histone modifications are massively lost across active genes, even with H3.3 deposition partially restoring nucleosome occupancy. ➡️Recycling of old modified histones through transcription is therefore critical to maintain active chromatin states.

5/7 A big surprise came when we looked at the 3d genome of FACT-depleted cells. Many highly-transcribed genes coalesce into 𝐚𝐛𝐞𝐫𝐫𝐚𝐧𝐭 𝐦𝐢𝐜𝐫𝐨-𝐜𝐨𝐦𝐩𝐚𝐫𝐭𝐦𝐞𝐧𝐭𝐬 (𝐀𝐌𝐂𝐬). These extended gene-gene interactions, not enriched for PolII & cohesion, led to our hypothesis that these interactions are affinity-driven.

2/7 We found that without FACT, replication and transcription quickly shutdown from defective progression through chromatin. With @jervdberg.bsky.social we saw that elongating replisomes stall globally within 1 hour of FACT depletion. After 24 hours, our FACT-depleted mouse ESCs are dead.

3/7 With @vram142.bsky.social‘s RASAM, we see the disruption of nucleosomes and their spacing in the wake of replication upon FACT depletion. The same is seen in the wake of transcription, but to a greater degree: chromatin fibre structure collapses ➡️ 𝐅𝐀𝐂𝐓 𝐢𝐬 𝐚 𝐮𝐧𝐢𝐯𝐞𝐫𝐬𝐚𝐥 𝐡𝐢𝐬𝐭𝐨𝐧𝐞 𝐫𝐞𝐜𝐲𝐜𝐥𝐞𝐫. ♻️

@marcelwerner.bsky.social

1/7 The FACT complex (SPT16 & SSRP1) is a histone chaperone involved in many processes including replication and transcription. This versatility has made untangling its functions in mammalian cells a challenge. Rapid degron-depletion of Spt16 allowed us to 𝐬𝐭𝐮𝐝𝐲 𝐭𝐡𝐞 𝐚𝐜𝐮𝐭𝐞 𝐞𝐟𝐟𝐞𝐜𝐭𝐬 𝐨𝐟 𝐅𝐀𝐂𝐓 𝐥𝐨𝐬𝐬.⚡

The Groth lab reposted

Marcel Werner

30 June

I am delighted to share that I have been awarded a Walter Benjamin Postdoctoral Fellowship from the @dfg.de to support my work in @grothlab.bsky.social at the Danish Cancer Institute. #DFG #cancerresearch #epigenetics

cell.comPost-replicative chromatin accessibility predicts cell fate changeKnudsen and colleagues use repli-ATAC-seq to compare replicated and unreplicated chromatin in two models of cell identity change. They find that lineage-specific elements are accessible earlier in rep...

25 Feb

DNA replication globally disrupts the epigenome. But does this create a chromatin-access opportunity for TF binding to facilitate cell identity change? Now 𝐫𝐞𝐩𝐥𝐢-𝐀𝐓𝐀𝐂-𝐬𝐞𝐪 shows 𝘥𝘦 𝘯𝘰𝘷𝘰 chromatin opening & TF binding occurs specifically post-replication, in cellular differentiation & reprogramming!

25 Feb

🧬 This work was a team effort from the Stewart-Morgan, Brickman & Groth labs👩‍🔬👨‍🔬🧑‍🔬 - great to see it now published! 📝 🥳

14 Jan

Congratulations to @groth-anja.bsky.social on receiving the Novo Nordisk Foundation Jacobæus Prize 🏆 we’re proud to see Anja's mentorship, leadership, & pioneering work in epigenetic cell memory getting top recognition 👏 celebrating the contributions of past & present lab members to this work too 🥳

novonordiskfonden.dkBiomedicine prize awarded to Professor Anja Groth for groundbreaking discoveries in epigenetic cell memory - Novo Nordisk Fonden

14 Jan

You can read more about Anja's award here: novonordiskfonden.dk/en/news/biom...

tinyurl.comRepair of DNA double-strand breaks leaves heritable impairment to genome functionUpon DNA breakage, a genomic locus undergoes alterations in three-dimensional chromatin architecture to facilitate signaling and repair. Although cells possess mechanisms to repair damaged DNA, it is ...

7 Nov 2025

Our latest collaboration with the talented Susi @sbantele.bsky.social and Jiri Lukas is out now @science.org 🤩. We reveal the hidden price for DNA repair, with potential implications for genome function, gene therapy and ageing👇

Susi Bantele@sbantele.bsky.social

𝗖𝗮𝗻 𝗰𝗲𝗹𝗹𝘀 𝗲𝘃𝗲𝗿 𝘁𝗿𝘂𝗹𝘆 𝗿𝗲𝗰𝗼𝘃𝗲𝗿 𝗳𝗿𝗼𝗺 𝗗𝗡𝗔 𝗱𝗮𝗺𝗮𝗴𝗲?Excited to share our new study “Repair of DNA double-strand breaks leaves heritable impairment to genome function”, revealing DNA repair’s hidden cost, out now @science.org tinyurl.com/5n6zw3ye. Led by @sbantele.bsky.social and Jiri Lukas.🧵👇1/n

28 Aug 2025

We have lift off!! 🚀 Yesterday was the official opening of EpiC! The DNRF Center for Epigenetic Cell Memory at the Danish Cancer Institute! Our EpiC team with director Anja Groth @groth-anja.bsky.social, were joined by Jesper Fisker, CEO @cancer.dk & Niels Mejlgaar, CEO @dg.dk to celebrate 🎉

@costalaboratory.bsky.social

28 Aug 2025

It was wonderful to hear talks from EpiC members @grothlab.bsky.social @nilskrietenstein.bsky.social @nilssonlab.bsky.social & Niels Mailand, now we are settled in our new home @cancer.dk. We are grateful for @dg.dk for this exciting opportunity. Onwards and upwards with EpiC science! 🧬 #CPRLegacy

The Groth lab reposted

Alessandro Costa

21 July 2025

Less than two weeks left to apply! Postdoc positions in my lab to study 1. initiation of DNA replication. 2. chromatin replication/epigenetic inheritance. Great for biochemists, biophysicists & structural biologists. Deadline 3 August 2025. crick.wd3.myworkdayjobs.com/External/job...

crick.wd3.myworkdayjobs.comPostdoctoral Fellow - Costa LabSalary for this Role: From £45,500 with benefits, subject to skills and experience. Job Title: Postdoctoral Fellow - Costa Lab Reports to: Alessandro Costa Closing Date: 03/Aug/2025 23.59 GMT Job Desc...

@costalaboratory.bsky.social

27 June 2025

Congratulations to Ada 🥳🍾, who very successfully defended her master's thesis today! You were an excellent student and we were super happy to have you in the lab! Wishing you all the best for the future and enjoy your well-deserved break!

The Groth lab reposted

Alessandro Costa

20 June 2025

Postdoc positions open in my lab (Francis Crick Institute) to study 1. initiation of DNA replication. 2. chromatin replication/epigenetic inheritance. Great for biochemists, biophysicists and cryo-EM/cryo-tomography scientists. Deadline 3 August 2025. crick.wd3.myworkdayjobs.com/External/job...

shorturl.atPostdoctoral Researcher - Computational modeling of Epigenetic Inheritance - 38 hours p/w - Hubrecht InstituteAbout the Project Faithful inheritance of the epigenome in proliferating cells critically underpins human development and health. While DNA replication fidelity and DNA mutation rates are well underst...

20 May 2025

🚨 Postdoc wanted (🇳🇱NL based) for our exciting collaboration with the lab of Alexander van Oudenaarden @hubrechtinstitute.bsky.social in Utrecht, with collaborative visits to our lab Copenhagen 🇩🇰. We seek a computational scientist to model epigenetic inheritance, see more below 👇!

Jeroen van den Berg@jervdberg.bsky.social

🧬Postdoc position alert! 🚨 We're hiring a postoc in Computational Modeling of Epigenetic Inheritance at the Hubrecht Institute (Alexander van Oudenaarden, Utrecht 🇳🇱) & Danish Cancer Institute (Anja Groth, Copenhagen 🇩🇰). Come work in our collaberative team of top scientists shorturl.at/avBBy

rdcu.beCODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supplyNature Communications - CODANIN-1 negatively regulates the function of ASF1, the key chaperone for histone H3-H4 supply. Here the authors present the cryo-EM structure of the CODANIN-1_ASF1A...

𝐍𝐞𝐰 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐭𝐢𝐜 𝐢𝐧𝐬𝐢𝐠𝐡𝐭𝐬 𝐢𝐧𝐭𝐨 𝐭𝐡𝐞 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐡𝐢𝐬𝐭𝐨𝐧𝐞 𝐬𝐮𝐩𝐩𝐥𝐲! Excited to share our latest collaboration led by tkjeong.bsky.social and ciaranfrater.bsky.social! Structural determination of the histone chaperone ASF1 and its regulator CODANIN-1 uncovers how CODANIN-1 counters ASF1 activity. 🧵👇

How important is CODANIN/ASF1A complex formation? Inhibiting dimerization in cells or introducing a pathogenic CDA-I mutation in the dimerization interface reduced ASF1A cytoplasmic sequestration. This shows the significance of CODANIN/ASF1A complex formation and possible disease relevance

Together our work gives a molecular basis for histone supply regulation by CODANIN-1, read the full paper here: rdcu.be/ecbHq . Thanks to the Song lab at KAIST jijoonsong.bsky.social for taking us onboard as collaborators for this exciting new structure-function adventure!

By binding in this way, CODANIN-1 occludes the two major histone-binding surfaces of ASF1A, preventing its chaperone activity. Interestingly, CODANIN-1 could also bind preformed ASF1A/H3-H4 using its B domains, suggesting that it may regulate ASF1 at multiple points in the histone supply chain.

Which CODANIN binding sites are required for ASF1 regulation? Using inducible complementation of CODANIN-1 in cells, we found that mutation of both BD-N and HMH-C is needed to prevent cytoplasmic sequestration of ASF1A. Thus, CODANIN-1 regulates ASF1A nuclear import by this dual-binding mechanism.

A bit of background: ASF1 plays a central role in histone nuclear import and supply for replication & transcription. CODANIN-1 is commonly mutated in a rare form of heritable anaemia (CDA-I) and inhibits histone supply by ASF1. But we don’t currently understand these roles on the molecular level.

embl.orgDNA replication and genome maintenance: from basic biology to disease

So, how does CODANIN-1 bind ASF1? Our cryo-EM structure reveals that CODANIN-1 forms a dimer, with each monomer binding two ASF1A molecules. These two ASF1As are held in proximal and distal positions by CODANIN’s N-terminal B domain (BD-N) and C-terminal histone H3 mimic helix (HMH-C), respectively.

The Groth lab reposted

Anja Groth

@groth-anja.bsky.social

26 Feb 2025

SAVE THE DATE! The next EMBO | EMBL Symposium on 'DNA replication and genome maintenance: from basic biology to disease' will be held October 20-23, 2026. Organized by Helle Ulrich (IMB), Johannes Walter (Harvard) and Anja Groth (Danish Cancer Institute). www.embl.org/about/info/c...

The Groth lab reposted

Robin Allshire 🇮🇪 🇪🇺✊🏿 ⬆️ Zak’s favourite nucleosome: K9me

@allshire-lab.bsky.social

25 Feb 2025

Epigenetics Gordon Research Conference. Consider joining us for what will be an excellent, exciting meeting and will be held in Europe for the first time: 10-15 Aug25 Barcelona, Spain. Please repost and apply early - this meeting is popular! www.grc.org/epigenetics-...

grc.org2025 Epigenetics Conference GRCThe 2025 Gordon Research Conference on Epigenetics will be held in Castelldefels, Barcelona Spain. Apply today to reserve your spot.

The Groth lab reposted

Marcel Werner

@marcelwerner.bsky.social

20 Feb 2025

I am delighted to share the main work of my PhD project in the @hamperllab.bsky.social now out in @narjournal.bsky.social. TRCs drive R-loop-dependent nucleosome eviction and require DOT1L activity for transcription recovery. academic.oup.com/nar/article/... #TRC #r-loop #chromatin More below 👇

academic.oup.comTranscription-replication conflicts drive R-loop-dependent nucleosome eviction and require DOT1L activity for transcription recoveryAbstract. Progressing transcription and replication machineries profoundly impact their underlying chromatin template. Consequently, transcription-replicat

tinyurl.comDisabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viabilityLosing parental histones during DNA replication fork passage challenges differentiation competence and cell viability.

𝐇𝐨𝐰 𝐝𝐨 𝐜𝐞𝐥𝐥𝐬 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐰𝐡𝐨 𝐭𝐡𝐞𝐲 𝐚𝐫𝐞 𝐚𝐟𝐭𝐞𝐫 𝐃𝐍𝐀 𝐫𝐞𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧? Our new study “Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability” is out in 𝘚𝘤𝘪𝘦𝘯𝘤𝘦 𝘈𝘥𝘷𝘢𝘯𝘤𝘦𝘴. Led by @lleonie.bsky.social @biranalva.bsky.social 🧵 More below👇

Want to dive deeper? 🧐 Read the full paper here: tinyurl.com/233y89d2 🔗📖. Last, a big thank you to all our collaborators and colleagues at #NNF-CPR 🙏. #HistoneRecycling #Epigenetics #Chromatin #ScienceAdvances 5/n

tinyurl.com6 Postdoctoral and PhD positions in Center for Epigenetic Cell Memory (EpiC)The Center for Epigenetic Cell Memory (EpiC) is a new Center of Excellence that will be established based on funding by the Danish National Research Foundation.

If you’re interested in epigenetic inheritance and cell division, check out the vacancies for 6 PhDs and Postdocs positions in our new Center for Epigenetic Cell Memory (EpiC): tinyurl.com/yvd93na2 6/n

What happens next? Gene misregulation & differentiation defects start to emerge. But when 𝐛𝐨𝐭𝐡 leading & lagging strand recycling are disrupted (POLE4 & MCM2-2A), 𝐬𝐨𝐦𝐞 𝐩𝐚𝐫𝐞𝐧𝐭𝐚𝐥 𝐡𝐢𝐬𝐭𝐨𝐧𝐞𝐬 𝐚𝐫𝐞 𝐥𝐨𝐬𝐭 𝐢𝐧 𝐭𝐫𝐚𝐧𝐬𝐦𝐢𝐬𝐬𝐢𝐨𝐧 —worsening the defects. Unlike single mutants, cells now start to die! 3/n

Our work highlights 𝐩𝐚𝐫𝐞𝐧𝐭𝐚𝐥 𝐡𝐢𝐬𝐭𝐨𝐧𝐞 𝐫𝐞𝐜𝐲𝐜𝐥𝐢𝐧𝐠 𝐚𝐬 𝐚 𝐤𝐞𝐲 𝐞𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐬𝐚𝐟𝐞𝐠𝐮𝐚𝐫𝐝 – histone modifications must be 𝐞𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐭𝐥𝐲 transmitted to 𝐛𝐨𝐭𝐡 daughter strands for this to work! Could failures in this process contribute to developmental disorders, cancer, or aging? More to explore! 4/n

During replication, modified parental histones are transmitted to the daughter DNA strands - they are recycled. Recycled histones serve as agents of memory to maintain the epigenome in daughter cells! What happens when recycling is acutely disrupted? 1/n

nilskrietenstein.bsky.social

We use a degron to deplete POLE4, a leading strand recycler, in WT or a background defective in lagging strand recycling (MCM2-2A). The first epigenome alteration upon acute loss of leading strand recycling is 𝐚𝐜𝐜𝐮𝐦𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐇𝟑𝐊𝟐𝟕𝐦𝐞𝟑 - 𝐰𝐢𝐭𝐡𝐢𝐧 𝟏-𝟐 𝐜𝐞𝐥𝐥 𝐜𝐲𝐜𝐥𝐞𝐬 - 𝐛𝐞𝐟𝐨𝐫𝐞 𝐭𝐫𝐚𝐧𝐬𝐜𝐫𝐢𝐩𝐭𝐢𝐨𝐧𝐚𝐥 𝐜𝐡𝐚𝐧𝐠𝐞𝐬! 2/n

The Groth lab reposted

@nilskrietenstein.bsky.social

12 Feb 2025

Replying to @grothlab.bsky.social

6 PhD and postdoc positions in the new Center for Epigenetic Cell Memory in Copenhagen, Denmark. Interested in epigenetics and chromatin b biology? Consider applying here: tinyurl.com/yvd93na2. Please share!!!

12 Feb 2025

🚨𝐌𝐚𝐣𝐨𝐫 𝐉𝐨𝐛 𝐀𝐥𝐞𝐫𝐭!🚨The Groth @groth-anja.bsky.social, Mailand, Nilsson @nilssonlab.bsky.social & Krietenstein @nilskrietenstein.bsky.social labs are hiring 𝟔 𝐏𝐡𝐃&𝐩𝐨𝐬𝐭𝐝𝐨𝐜𝐬 to join the new Center for Epigenetic Cell Memory (EpiC) in Copenhagen, Denmark. Apply here: tinyurl.com/yvd93na2 & please share!

hubrecht.euVan Oudenaarden and Groth research groups receive Novo Nordisk Foundation Synergy Grant for Epigenome Fidelity - Hubrecht Institute

12 Feb 2025

More info here:

The Groth lab reposted

Jeroen van den Berg

@jervdberg.bsky.social

21 Jan 2025

Do not miss out on this webinar on @bio-protocol.bsky.social to see what we have been up to in quantifiying single cell DNA replication dynamics using scEdU-seq ! 🚀 Register now! bio-protocol.org/webinar/deta...

The Groth lab reposted

Jeroen van den Berg

@jervdberg.bsky.social

20 Dec 2024

Just over the moon that the grant, wrote with my amazing long-time friend @lleonie.bsky.social, has been funded by @novo-nordisk.bsky.social for an incredible €2M! 🤯 Huge thanks to Alexander and @grothlab.bsky.social for their support and guidance throughout. Thrilled for the journey ahead! 🎆✨

Hubrecht Institute@hubrechtinstitute.bsky.social

How reliably is the epigenome passed from one cell to its daughter cells? Alexander van Oudenaarden @jervdberg.bsky.social @grothlab.bsky.social @lleonie.bsky.social received @novo-nordisk.bsky.social grant to study this question ➡️new strategies to prevent disease & combat aging tinyurl.com/yh925b9u

hubrecht.euVan Oudenaarden and Groth research groups receive Novo Nordisk Foundation Synergy Grant for Epigenome Fidelity - Hubrecht Institute

20 Dec 2024

Exciting news!🌟 Together with Alexander van Oudenaarden, @jervdberg.bsky.social and @lleonie.bsky.social, we’ve been awarded a €2M NNF Synergy grant. We're thrilled to collaborate🤝 and to develop cutting-edge single-cell and single-molecule methods for replication and chromatin research! 🚀

Hubrecht Institute@hubrechtinstitute.bsky.social

5 Dec 2024

This is a reminder that there is still space in this starter pack if you want to join 🤩. Just send us a message!

The Groth lab@grothlab.bsky.social

Please join this starter pack for everyone working from chromatin replication to epigenetic inheritance and cell fate! Now still small, but we hope to gather everyone interested in joining. Please message us to be added, go.bsky.app/ALFFRUN

26 Nov 2024

The Groth lab reposted

Maxim Greenberg

@maxvcg.bsky.social

26 Nov 2024

Very happy to see @grothlab.bsky.social , @helink.bsky.social and @grewalsh.bsky.social all migrating over here! All pillars of the the #epigenetics and chromatin community.

25 Nov 2024

The Groth lab @grothlab.bsky.social has also made the jump from X to Bluesky🤩! Please follow us for all things related to chromatin replication, epigenetic memory and (epi)genome stability in the context of mitotic cell division! We'll start on joining some relevant starter packs!

25 Nov 2024

ICYMI: In spring 2025 the Groth lab is leaving CPR and moving to the Danish Cancer Institute along with the Mailand, Nilsson and Krietenstein labs to establish a Center of Excellence with a focus on Epigenetic Cell Memory (EpiC) 🤩