8/ We propose that H3K27me3 mimicry has repeatedly emerged through evolution to restrict the spread of Polycomb domains by breaking the PRC2-H3K27me3 positive feedback loop.
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7/ We find that the allosteric regulatory activities of JARID2 and PALI1 synergise to antagonise PRC2 during mouse development and restrict the spread of Polycomb domains in mECS.
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6/ Unexpectedly, the H3K27me3 mimicry-defective JARID2 K116R exhibited a homeotic transformation characteristics of Polycomb gain-of-function!
This seemingly goes against the prevalent paradigm where JARID2 K116me3 is believed to positively regulate PRC2.
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5/ To determine what is the function of H3K27me3 mimicry, we used CRISPR/Cas to generate 3 knock-in mouse lines: each included a single K-to-R mutation that specifically prevents JARID2, PALI1 or PALI2 from mimicking H3K27me3.
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a black and white photo of a man working on a car .
ALT: a black and white photo of a man working on a car .
4/ Why do JARID2 and PALI1/2 mimic H3K27me3? They are thought to "jump start" PRC2 in the absence of H3K27me3, to initiate H3K27me3 de novo. While this model agrees with biochemical and KO+rescue experiments in cells, it was never tested in vivo.
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3/ H3K27me3 binds to PRC2. Some proteins mimic H3K27me3 to directly interact with the H3K27me3-binding site in PRC2.
- The Margueron lab showed it for JARID2: pmc.ncbi.nlm.nih.gov/articles/PMC...
- We showed it for PALI1/2: www.nature.com/articles/s41...
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1/ H3K27me3 mimicry has repeatedly emerged through evolution, but what's the physiological relevance?
We show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2 in vivo and restrict the spread of Polycomb domains.
🧵
www.biorxiv.org/content/10.1...
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I am recruiting a postdoc with experience in Protein Biochemistry, Structural Biology & Chromatin Biology. If you are passionate about the complex world of chromatin modifications, please contact me for more details 🙏.
Location: SAiGENCI, Adelaide, Australia
🦘🍷🏄🏖️🇦🇺
10.12.2024 05:12 — 👍 20 🔁 17 💬 2 📌 1
Developing the next generation of Australian life science leaders through national & international collaboration 👩🔬 🔬🌏 www.emblaustralia.org
Research associate in the Robert Lab @ircm.bsky.social interested in chromatin and gene regulation. she/her
Group leader, transcription dynamics in single cells, NKI
Sigrid Jusélius Professor, Translational Cancer Medicine Program & Department of Biochemistry and Developmental Biology, University of Helsinki, Finland. #cancer #genomics #transcription #chromatin
Physician-scientist at Stanford Med, loves bones.
Chief, Division of Endocrinology | Vice Chair of Basic Science, Department of Medicine | ASBMR Councilor
MD/Leu-chemist, now learning immunology/virology.(PhDc)
Principal Investigator APC microbiome Ireland, Lecturer Anatomy and Neuroscience University College Cork #microglia #glioma #gut-brain-axis #DIPG #chadtough
PhD Student in BioEngg @ IISc | Studying biological networks, gene regulation, and cellular decision-making through computational models.
moltenecdysone09.github.io
Professor studying how genetic information is passed down to the next generation | She/Her | 🇮🇹 expat in the 🇺🇸 | Wannabe 🐎 rider | She/her | Posts and likes=mine
When I grow up, I want to be a scientist. Postoc in @grothlab.bsky.social. Fond of chromatin biology, DNA replication, space, pandas, and more. PhD from @lab-hat.bsky.social.
Epigenetics, transposable elements, plant biology.
Postdoc @ Gregor Mendel Institute (Vienna, Austria).
@gmivienna.bsky.social
Epigeneticist made of glitter and sunscreen. I live for music and travel but love squished pennies, purple, and tardigrades.
Opinions are my own.
Physician-scientist @danafarber.bsky.social studying MDS, AML, and bone marrow failure; Director, Edward P. Evans Center for MDS.
lindsleylab.dana-farber.org
Professor for Pharmacology, Uni Graz; Group leader, Uni Freiburg @uni-freiburg.de; previously Center for Epigenomics at UCSD @ucsdepigenomics.bsky.social; epigenomics, technologies, aging, heart, kidney, macrophages
Painting, reading, traveling, I want to be able to travel all over the world in my lifetime
A person who loves life, currently living in Portland, Oregon, USA
I love technology and believe that technology can change the world and mak
Group leader @IGBMC - Permanent researcher @CNRS - Computational regulatory genomics
I talk about computational #openscience communication and science publishing. On the jupyterbook.org & @mystmd.org teams, co-founder of @curvenote.com & @continuous.foundation.
