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👇 - ThreadSky

grothlab.bsky.social • 80 days ago

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👇

Comments

grothlab.bsky.social•80 days ago

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

grothlab.bsky.social•80 days ago

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

grothlab.bsky.social•80 days ago

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

grothlab.bsky.social•80 days ago

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

grothlab.bsky.social•80 days ago

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

grothlab.bsky.social•80 days ago

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): https://tinyurl.com/yvd93na2 6/n

alessandrodonada.bsky.social•80 days ago

I'll definitely dive into this work! Love the premise, and very curious about the methods!

meshorer.bsky.social•78 days ago

Congrats Anja, Leonie and Alva! Beautiful work🥂

robklose.bsky.social•80 days ago

Congratulations Anja and team. Look forward to reading!

fmattiroli.bsky.social•79 days ago

Congratulations!! Great to see this out! 👏

almassalha.bsky.social•80 days ago

Just curious, what are the long genes doing when the replication mediated deposition is disrupted?

lleonie.bsky.social•78 days ago

We don't find that they are susceptible to disrupted histone recycling. There is no correlation between gene length and changes in gene expression in our recycling mutants.

almassalha.bsky.social•78 days ago

Interesting, this gives me a lot to think about. That was the case both in general and with the RA induced differentiation?

lleonie.bsky.social•78 days ago

Yes

almassalha.bsky.social•78 days ago

Thanks for checking, this is really helpful!

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