Qi Zhang

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.

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.

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.

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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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.

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...

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains The Polycomb repressive complex 2 (PRC2) is essential for normal development by maintaining developmental gene repression. PRC2 deposits the repressive chromatin mark H3 lysine 27 tri-methyl (H3K27me3...

2/ Credit first: Led by Samuel Agious, a PhD student in the @davidovichlab.bsky.social, @monashuniversity.bsky.social, through collaboration with the Eddy McGlinn lab.
www.biorxiv.org/content/10.1...

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

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
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Modular cloning of multigene vectors for the baculovirus system and yeast Recombinant macromolecular complexes are often produced by the baculovirus system, using multigene expression vectors. Yet, the construction of baculovirus-compatible multigene expression vectors is c...

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