Shiv Grewal

Thanks Maharshi!

Thanks Amritesh!

Heterochromatin self-propagation is actively regulated by H3K14-ub in response to external stimuli, with broad implications for rapid changes in the epigenetic landscape in physiology and disease @nature.com @grewalsh.bsky.social @ncicancer.bsky.social
www.nature.com/articles/s41...

9/ Big picture: heterochromatin inheritance is actively regulated.
Given extensive heterochromatin remodeling in development and cancer, this opens new ways to think about how epigenetic landscapes are rewired in disease

8/ In fungi, this system promotes resistance to antifungal drugs by adjusting heterochromatin spreading - highlighting its physiological relevance

7/ Remarkably, this pathway is wired into environmentally responsive signaling networks, including TOR and NMD, allowing cells to modulate heterochromatin inheritance in response to external conditions 🌍

6/ The HRH is tuned by the dosage of a substrate receptor for an E3 ubiquitin ligase, promoting histone H3K14 mono-ubiquitination (H3K14ub) - a modification essential for efficient H3K9me3 and heterochromatin self-propagation

5/ In our new work, we identify a heterochromatin heritability regulatory hub (HRH) - a ubiquitin-dependent pathway that broadly controls heterochromatin propagation across chromosomal contexts

4/But one big question remained 👇
Do external cues regulate heterochromatin spreading and inheritance?

3/ In this mechanism, critical density of H3K9me3 modified histones recruit histone methyltransferases that deposit more of the same mark-allowing epigenetic inheritance through cell division - maintaining cell identity and preventing de-differentiation

2/ Repressive heterochromatin is nucleated at specific genomic sites, then spreads across large chromosomal domains.
Key to this is a self-templating “read–write” mechanism (PMID: 18345014)

1/ How is heterochromatin spread and epigenetically inherited as cells divide and how do external cues tune this process?
Our previous work laid the foundation. Here’s what we knew and what we’ve now uncovered ⬇️

Read in Nature: nature.com/articles/s41586-025-09899-8

Stress controls epigenetic inheritance!

A histone ubiquitylation-based regulatory hub links stress/environmental signaling to heterochromatin self-propagation and epigenetic inheritance-reshaping how we think about development, drug resistance, and cancer
👉 nature.com/articles/s41586-025-09899-8

It was wonderful to host Shiv Grewal @grewalsh.bsky.social from NIH earlier this week. Shiv gave a beautiful talk on heterochromatin propagation and the epigenetic landscape. We had a stimulating discussion after his lecture. It was also great to have him visit my single-molecule biophysics lab.

Congratulations!

The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate - Nature Cell Biology Marin et al. report the role of lamin proteins and the lamin B receptor (LBR) in chromatin positioning at the nuclear periphery. Knockout of all lamins and LBR in mouse embryonic stem cells leads to h...

Another paper bluetorial! Today: how does the spatial location of genes influence their function? (1/n) www.nature.com/articles/s41...

Grateful for the warm welcome @tifrhyderabad.bsky.social :) Thrilled to be part of this vibrant scientific community and eager to build an exciting research program!

So proud of you, @sahanaholla! Watching your journey has been such a joy. Wishing you all the best as you begin this exciting new chapter at TIFRH. They’re lucky to have you!

Remembering Dave’s goodness gives me hope every day.

It was an honor to speak at the Rockefeller University symposium celebrating David Allis—a true visionary who transformed the field of chromatin and gene expression. His legacy continues to inspire us all. Grateful to the organizers for such a meaningful and inspiring event.

AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development Argonaute (AGO) mediated slicing of RNA, also known as RNAi, is a highly conserved phenomenon that is evolutionarily linked to the repression of transposons and other repeats. Although RNAi is no long...

What was that you said? You are looking for new #RNA research to read in the weekend?

You are in luck!

📣 📣 Check out the new preprint from our lab!!!! 📣 📣

www.biorxiv.org/content/10.1...

Who does that? We rented a train JUST for the conference, that will take the participants from Prague to the woods of Bohemia. There'll be talks ON THE TRAIN. In Prague we'll have 5 locations with different atmospheres.
#theconferencetoendallconferences Register now:
woodstock.img.cas.cz

Congratulations Aaron! Well deserved!

Wishing your daughter and your entire family all the very best!

What RNA polymerase gets up to in the genome and how mutations happen! Just out in Nature! Many thanks to many collaborators & congrats 1st author Jingjing Liu! www.nature.com/articles/s41...

Deeply saddened to learn of Scott’s passing. His legacy lives on through his impactful scientific contributions and the many people he mentored. My thoughts are with his family and loved ones during this difficult time.

Our collaboration with the Muir lab revealed that N-terminal histone modifications can 'detoxify' K27M inhibition by altering PRC2-substrate interactions. Acetylation showed the greatest impact, supported by xenograft data from the Monje group. pubs.acs.org/doi/epdf/10....

Dynamic PRC1–CBX8 stabilizes a porous structure of chromatin condensates - Nature Structural & Molecular Biology Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility an...

We used cryoET and biophysical approaches in vitro together with molecular biology in differentiated cells to show that chromatin compacted by PRC1-CBX8 is porous and accessible while PRC1 is dynamic in it. 🧪🧬 #cryoET #Epigenetics #Polycomb www.nature.com/articles/s41...

Deeply saddened by the news of Sergio Pimpinelli’s passing. A brilliant scientist, his groundbreaking research and the countless lives he inspired will ensure his legacy endures.

🎉 CONGRATULATIONS to Manjit Srivastav, Diego Folco, Patroula Nathanailidou, Anupa Anil, Drisya Vijaykumari, Shweta Jain, Jothy Dhakshnamoorthy, David Wheeler, and our amazing collaborators Maura O’Neill and Thorkell Andresson! Your unwavering dedication, hard work, and passion are truly inspiring 🙌✨