Explanipedia

Auto-inhibition of PRC2 by the broadly expressed long isoform of AEBP2 Open

Marlena Mucha, Zhihao Lai, Nicholas Mckenzie, Francesca Matrà, Marion Boudes , et al. · 2025

Polycomb Repressive Complex 2 (PRC2) is an essential chromatin regulator responsible for mono-, di- and tri-methylating H3K27. Control of PRC2 activity is a critical process in development and disease, yet no inhibitory cofactor has been i…

Dominant-negative effects of Weaver syndrome-associated EZH2 variants Open

Orla Deevy, Jingjing Li, Craig Monger, Francesca Matrà, Ellen Tuck , et al. · 2025

Heterozygous missense mutations in EZH2 cause Weaver syndrome (WS), a developmental disorder characterized by intellectual disability and overgrowth. EZH2 encodes the enzymatic subunit of Polycomb repressive complex 2 (PRC2), which mediate…

MORC2 is a phosphorylation-dependent DNA compaction machine Open

Winnie Tan, J.-G. Park, Hariprasad Venugopal, Jieqiong Lou, Prabavi Shayana Dias , et al. · 2025

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains Open

Samuel C. Agius, Marion Boudes, Evan Healy, Yi-Cheng Chang, M. Murray , et al. · 2025

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) through a read-write loop that involv…

Dynamic PRC1–CBX8 stabilizes a porous structure of chromatin condensates Open

Michael Uckelmann, Vita Levina, Cyntia Taveneau, Xiao Han Ng, Varun Pandey , et al. · 2025

The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin c…

Modular Cloning of Multigene Vectors for the Baculovirus System and Yeast Open

Zhihao Lai, Sarena F. Flanigan, Marion Boudes, Chen Davidovich · 2025

Recombinant macromolecular complexes are often produced by the baculovirus system, using multigene expression vectors. Yet, the construction of baculovirus-compatible multigene expression vectors is complicated and time-consuming. Furtherm…

A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells Open

Rachel McCole, James Nolan, David M Reck, Craig Monger, Samantha Rustichelli , et al. · 2025

Polycomb repressive complex 2 (PRC2), composed of the core subunits EED, SUZ12, and either EZH1 or EZH2, is critical for maintaining cellular identity in multicellular organisms. PRC2 deposits H3K27me3, which is thought to recruit the cano…

Modular cloning of multigene vectors for the baculovirus system and yeast Open

Zhihao Lai, Sarena F. Flanigan, Marion Boudes, Chen Davidovich · 2024

Recombinant macromolecular complexes are often produced by the baculovirus system, using multigene expression vectors. Yet, the construction of baculovirus-compatible multigene expression vectors is complicated and time-consuming. Furtherm…

Advancing microRNA target site prediction with transformer and base-pairing patterns Open

Yue Bi, Fuyi Li, Cong Wang, Tong Pan, Chen Davidovich , et al. · 2024

MicroRNAs (miRNAs) are short non-coding RNAs involved in various cellular processes, playing a crucial role in gene regulation. Identifying miRNA targets remains a central challenge and is pivotal for elucidating the complex gene regulator…

Histone H3.3 lysine 9 and 27 control repressive chromatin at cryptic enhancers and bivalent promoters Open

Matteo Trovato, Daria Bunina, Umut Yildiz, Nadine Fernandez-Novel Marx, Michael Uckelmann , et al. · 2024

Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutate histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here…

MORC2 phosphorylation fine tunes its DNA compaction activity Open

Winnie Tan, Jeong Veen Park, Hariprasad Venugopal, Jie Qiong Lou, Prabavi Shayana Dias , et al. · 2024

Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of MORC2, frequently phosphorylated in DNA damage, promo…

Inseparable RNA binding and chromatin modification activities of a nucleosome-interacting surface in EZH2 Open

Emma H. Gail, Evan Healy, Sarena F. Flanigan, Natasha Jones, Xiao Han Ng , et al. · 2024

Advancing microRNA Target Site Prediction with Transformer and Base-Pairing Patterns Open

Yue Bi, Fuyi Li, Cong Wang, Tong Pan, Chen Davidovich , et al. · 2024

Micro RNAs (miRNAs) are short non-coding RNAs involved in various cellular processes, playing a crucial role in gene regulation. Identifying miRNA targets remains a central challenge and is pivotal for elucidating the complex gene regulato…

Chromatin compaction by Polycomb group proteins revisited Open

Michael Uckelmann, Chen Davidovich · 2024

The chromatin compaction activity of Polycomb group proteins has traditionally been considered essential for transcriptional repression. However, there is very little information on how Polycomb group proteins compact chromatin at the mole…

The apparent loss of PRC2 chromatin occupancy as an artifact of RNA depletion Open

Evan Healy, Qi Zhang, Emma H. Gail, Samuel C. Agius, Guizhi Sun , et al. · 2024

RNA has been implicated in the recruitment of chromatin modifiers, and previous studies have provided evidence in favor and against this idea. RNase treatment of chromatin is commonly used to study RNA-mediated regulation of chromatin modi…

The apparent loss of PRC2 chromatin occupancy as an artefact of RNA depletion Open

Evan Healy, Qi Zhang, Emma H. Gail, Samuel C. Agius, Guizhi Sun , et al. · 2023

RNA has been implicated in the recruitment of chromatin modifiers, and previous studies have provided evidence in favour and against this idea. RNase treatment of chromatin is a prevalent tool for the study of RNA-mediated regulation of ch…

Dominant negative effects on H3K27 methylation by Weaver syndrome-associated EZH2 variants Open

Orla Deevy, Craig Monger, Francesca Matrà, Ellen Tuck, Eric Conway , et al. · 2023

Heterozygous missense mutations in EZH2 cause Weaver syndrome (WS), a developmental disorder characterized by intellectual disability and overgrowth. EZH2 encodes the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which mediate…

Histone H3.3 lysine 9 and 27 control repressive chromatin states at cryptic<i>cis</i>-regulatory elements and bivalent promoters in mouse embryonic stem cells Open

Matteo Trovato, Daria Bunina, Umut Yildiz, Nadine Fernandez-Novel Marx, Michael Uckelmann , et al. · 2023

Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutated histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Her…

Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates Open

Michael Uckelmann, Vita Levina, Cyntia Taveneau, Xiao Han Ng, Varun Pandey , et al. · 2023

The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organisation and dynamics of chromatin c…

H2A Ubiquitination Alters H3-tail Dynamics on Linker-DNA to Enhance H3K27 Methylation Open

Hideaki Ohtomo, Shinsuke Ito, Nicholas Mckenzie, Michael Uckelmann, Masatoshi Wakamori , et al. · 2023

Polycomb repressive complex 1 (PRC1) and PRC2 are responsible for epigenetic gene regulation. PRC1 ubiquitinates histone H2A (H2Aub), which subsequently promotes PRC2 to introduce the H3 lysine 27 tri-methyl (H3K27me3) repressive chromatin…

Cryo electron tomography of chromatin condensed by PRC1-CBX8 Open

Michael Uckelmann, Vita Levina, Cyntia Taveneau, de Marco A, Chen Davidovich · 2022

DNA binding by polycomb-group proteins: searching for the link to CpG islands Open

Brady M. Owen, Chen Davidovich · 2022

Polycomb group proteins predominantly exist in polycomb repressive complexes (PRCs) that cooperate to maintain the repressed state of thousands of cell-type-specific genes. Targeting PRCs to the correct sites in chromatin is essential for …

Origin of life: protoribosome forms peptide bonds and links RNA and protein dominated worlds Open

Tanaya Bose, G. Fridkin, Chen Davidovich, Miri Krupkin, Nikita Bhupesh Dinger , et al. · 2022

Although the mode of action of the ribosomes, the multi-component universal effective protein-synthesis organelles, has been thoroughly explored, their mere appearance remained elusive. Our earlier comparative structural studies suggested …

Structural basis of rotavirus RNA chaperone displacement and RNA annealing Open

Jack P. K. Bravo, Kira Bartnik, Luca Venditti, Julia Acker, Emma H. Gail , et al. · 2021

Significance Accurate RNA folding is essential for virus replication. Rotaviruses are viruses infecting humans and animals. Rotavirus genome comprises 11 distinct RNAs, and successful replication requires the incorporation of all 11 RNAs i…

Structural basis of rotavirus RNA chaperone displacement and RNA annealing. Open

Jack P. K. Bravo, Kira Bartnik, Luca Venditti, Julia Acker, Emma H. Gail , et al. · 2021

Rotavirus genomes are distributed between 11 distinct RNA molecules, all of which must be selectively copackaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP2. He…

PALI1 facilitates DNA and nucleosome binding by PRC2 and triggers an allosteric activation of catalysis Open

Qi Zhang, Samuel C. Agius, Sarena F. Flanigan, Michael Uckelmann, Vitalina Levina , et al. · 2021

Allosteric regulation of histone lysine methyltransferases: from context-specific regulation to selective drugs Open

Chen Davidovich, Qi Zhang · 2021

Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, wit…

Structural basis of rotavirus RNA chaperone displacement and RNA annealing Open

Jack P. K. Bravo, Kira Bartnik, Luca Venditti, Emma H. Gail, Chen Davidovich , et al. · 2020

Rotavirus genomes are distributed between eleven distinct RNA molecules, all of which must be selectively co-packaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP…

Convergent evolution between PALI1 and JARID2 for the allosteric activation of PRC2 Open

Qi Zhang, Samuel C. Agius, Sarena F. Flanigan, Vitalina Levina, Brady M. Owen , et al. · 2020

The polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identities. JARID2 is the only accessory subunit of PRC2 that known to trigger an allosteric activation of methyltransferase. Yet, this mechanism c…

Structural basis of specific H2A K13/K15 ubiquitination by RNF168 Open

Velten Horn, Michael Uckelmann, Heyi Zhang, Jelmer Eerland, Ivette Aarsman , et al. · 2019

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