"These data show that a reversible depletion of #Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through #epigenetic dysregulation leading to inheritance of altered cell fates"

https://www.nature.com/articles/s41586-024-07328-w

#cancer #oncology

A nice paper is the best way to start the year: here evidence that the #Polycomb PRC1 complex is required to maintain the undifferentiated state of adult spermatogonia stem cells.

Nucleic Acids Res. 2023 Dec 24
doi: 10.1093/nar/gkad1203.

PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation

Happy New Year: Peace, Joy, Health and Love for everybody !

An analysis of the interplay between #Polycomb proteins and 3D #genome modulation by loop extrusion. Read here:

Nat Commun. 2023
doi: 10.1038/s41467-023-43869-w.

Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops

In the paper below, exciting discussion on the evolution of #Polycomb complexes:

Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1

Commun Biol. 2023 Nov 10;6(1):1144.
doi: 10.1038/s42003-023-05501-x

Seung Kim, Frederick Dick et al show that resting #Bcells are uniquely sensitive to #EZH2 #polycomb complex inhibition, which activates expression of repetitive genomic elements and subsequent #innateimmune receptor signaling in a form of viral mimicry

https://www.embopress.org/doi/full/10.15252/embj.2023114462

A universal #aging clock based on #DNA methylation profiles and linked to #Polycomb proteins:

doi: 10.1038/s43587-023-00462-6.

Universal DNA methylation age across mammalian tissues

The authors conclude: Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

A new study from Yuri Schwartz's lab:

#Polycomb proteins translate #histone #methylation to #chromatin
folding

DOI: 10.1016/j.jbc.2023.105080

Exciting work from Wendy Bickmore's lab on the relation between phase separation and #Polycomb:

Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops

doi: 10.26508/lsa.202302101.

Here the authors identify a protein that might promote cancer by inhibiting #Polycomb PRC2-mediated deposition of H3K27me3.

NOP16 is a histone mimetic that regulates Histone H3K27 methylation and gene repression

DOI: 10.1101/2023.06.13.544862

A famous #Polycomb protein with roles in gene silencing but also activation!

BMI1 fine-tunes gene repression and activation to safeguard undifferentiated spermatogonia fate

Front. Cell Dev. Biol., Volume 11 - 2023

https://doi.org/10.3389/fcell.2023.1146849

Here the identification of yet another recruiter of #Polycomb group proteins in #Drosophila, great work from the Erokhin, Chetverina and Kassis labs !

Crol contributes to PRE-mediated repression and Polycomb group proteins recruitment in Drosophila, Nucleic Acids Research, 2023; gkad336, https://doi.org/10.1093/nar/gkad336

An unexpected twist between #Polycomb and #Notch signaling: a PRC2 enzyme induces Notch signaling using non-enzymatic functions.

Feng, X., Wang, A.H., Juan, A.H., Ko, K.D., Jiang, K., Riparini, G., Ciuffoli, V., Kaba, A., Lopez, C., Naz, F., et al. (2023). Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling. Dev Cell. 10.1016/j.devcel.2023.04.005.

Read this study from the labs of Zachary Smith and Alex Meissner on the of the interplay between #Polycomb silencing and #DNAmethylation to maintain gene silencing in extra-embryonic tissues:

Dynamic antagonism between key repressive pathways maintains the placental #epigenome.

Nat Cell Biol (2023). https://doi.org/10.1038/s41556-023-01114-y

Identification of new readers of bivalent chromatin in Arabidopsis:

A pair of readers of bivalent chromatin mediate formation of #Polycomb-based “memory of cold” in plants - https://doi.org/10.1016/j.molcel.2023.02.014

Here an interesting review on the interest and use of superresolution #microscopy in #Polycomb biology:

Biology (Basel). 2023 Feb 26;12(3):374.
doi: 10.3390/biology12030374.

On the Advent of Super-Resolution Microscopy in the Realm of Polycomb Proteins

Structural biology insights into a #Polycomb complex and its inhibition. Structural basis for inactivation of PRC2 by G-quadruplex RNA https://www.biorxiv.org/content/10.1101/2023.02.06.527314v1

PROTAC degraders Rock! Read this application to the #Polycomb BMI and RING1B proteins:
Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy.
https://doi.org/10.1002/advs.202205573

New discoveries about #Polycomb #EZH2 function in #MultipleMyeloma and a therapeutic avenue here:
Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader. Oncogene (2023). https://doi.org/10.1038/s41388-023-02618-5

Here, an interesting review specifically addressing the role of phosphorylation of the key #Polycomb PRC2 enzymatic subunit EEZH2 in #prostate #cancer: Beyond expression: role of phosphorylated residues of EZH2 in lineage plasticity in prostate cancer https://academic.oup.com/endo/advance-article-abstract/doi/10.1210/endocr/bqad023/7010689

#BRD4-#PRC2 represses #transcription of T-helper 2-specific negative regulators during #Tcell #differentiation:
Brd4 interacts with #Polycomb repressive complex 2 (PRC2) to repress transcriptional expression of T-helper 2 (Th2)-negative regulators #Foxp3 and E3 #ubiqutin #ligase #Fbxw7 during lineage-specific differentiation of #Th2 cells from mouse primary naïve CD4+ T cells
https://www.embopress.org/doi/10.15252/embj.2022111473