Article
Multidisciplinary Sciences
Jia-Ray Yu, Gary LeRoy, Devin Bready, Joshua D. Frenster, Ricardo Saldana-Meyer, Ying Jin, Nicolas Descostes, James M. Stafford, Dimitris G. Placantonakis, Danny Reinberg
Summary: The study identified that H3K36me2 promotes tumorigenesis in H3K27M-DIPG by affecting the writing activity of NSD1 and NSD2, as well as the reading factors LEDGF and HDGF2. Loss of NSD1/2 impedes cellular proliferation and tumorigenesis.
Article
Immunology
Annette E. Neele, Hung-Jen Chen, Marion J. J. Gijbels, Saskia van der Velden, Marten A. Hoeksema, Marieke C. S. Boshuizen, Jan Van den Bossche, Anton T. Tool, Hanke L. Matlung, Timo K. van den Berg, Esther Lutgens, Menno P. J. de Winther
Summary: Research indicates that myeloid EZH2 deficiency affects neutrophil migration and reduces macrophage foam cell inflammatory responses, contributing to the reduction of atherosclerosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Ludivine Raby, Pamela Volkel, Shaghayegh Hasanpour, Julien Cicero, Robert-Alain Toillon, Eric Adriaenssens, Isabelle Van Seuningen, Xuefen Le Bourhis, Pierre-Olivier Angrand
Summary: This study reports on a zebrafish line with a null allele of eed, a key component of PRC2, and reveals severe defects in digestive organs and brain neuronal differentiation in homozygous eed-deficient mutants, leading to death. Additionally, loss of PRC2 function in zebrafish increases larval activity and highlights its potential as a model for studying human pathologies linked to PRC2 dysfunction and reduced H3K27me3 levels.
Article
Cell Biology
Elsa Franco-Echevarria, Mathias Nielsen, Anna Schulten, Jitender Cheema, Tomos E. Morgan, Mariann Bienz, Caroline Dean
Summary: Polycomb repressive complex 2 (PRC2) mediates epigenetic silencing of target genes in animals and plants. In Arabidopsis, PRC2 relies on VEL accessory factors, including VRN5 and VIN3, to silence the FLC floral repressor locus under cold conditions. Our study reveals the distinct roles of VEL proteins in this process.
GENES & DEVELOPMENT
(2023)
Article
Medicine, Research & Experimental
Fei-Fei Hu, Hao Chen, Yang Duan, Bei Lan, Chun-Jie Liu, Hui Hu, Xu Dong, Qiong Zhang, Yi-Ming Cheng, Min Liu, An-Yuan Guo, Chenghao Xuan
Summary: The study reveals the oncogenic role of CBX2 and EZH2 in promoting lung adenocarcinoma progression, and suggests that the combination of high expression of CBX2 and EZH2 indicates poor prognosis in lung adenocarcinoma. Inhibition of both CBX2 and EZH2 synergistically suppresses the growth and metastasis of lung adenocarcinoma cells.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Chemistry, Medicinal
Rohan Kalyan Rej, Changwei Wang, Jianfeng Lu, Mi Wang, Elyse Petrunak, Kaitlin P. Zawacki, Donna McEachern, Chao-Yie Yang, Lu Wang, Ruiting Li, Krishnapriya Chinnaswamy, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Yunlong Zhou, Jianyong Chen, Guozhi Tang, Shaomeng Wang
Summary: The discovery of exceptionally potent and efficacious EED inhibitors has demonstrated significant potential for the treatment of human cancers and other diseases. Through optimization and structural studies, a promising compound, EEDi-5273, has shown excellent inhibitory effects on tumor growth in experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Robbie G. Majzner, Sneha Ramakrishna, Kristen W. Yeom, Shabnum Patel, Harshini Chinnasamy, Liora M. Schultz, Rebecca M. Richards, Li Jiang, Valentin Barsan, Rebecca Mancusi, Anna C. Geraghty, Zinaida Good, Aaron Y. Mochizuki, Shawn M. Gillespie, Angus Martin Shaw Toland, Jasia Mahdi, Agnes Reschke, Esther H. Nie, Isabelle J. Chau, Maria Caterina Rotiroti, Christopher W. Mount, Christina Baggott, Sharon Mavroukakis, Emily Egeler, Jennifer Moon, Courtney Erickson, Sean Green, Michael Kunicki, Michelle Fujimoto, Zach Ehlinger, Warren Reynolds, Sreevidya Kurra, Katherine E. Warren, Snehit Prabhu, Hannes Vogel, Lindsey Rasmussen, Timothy T. Cornell, Sonia Partap, Paul G. Fisher, Cynthia J. Campen, Mariella G. Filbin, Gerald Grant, Bita Sahaf, Kara L. Davis, Steven A. Feldman, Crystal L. Mackall, Michelle Monje
Summary: Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are lethal pediatric tumors of the central nervous system. GD2-directed chimeric antigen receptor (CAR) T cells show promising preclinical efficacy. Four patients with H3K27M-mutated DIPG or spinal cord DMG were treated with GD2-CAR T cells and showed clinical and radiographic improvement.
Article
Oncology
Xiao Mu Hu, Xiao yu Nie, Kai lun Xu, Yin Wang, Feng Tang, Zun guo Du, Ji Xiong
Summary: Diffuse midline glioma (DMG), H3K27 altered, mainly occurs in the thalamus in adult patients, with H3K27M mutations more commonly found in young adults and leading to a worse prognosis. Age is the only independent prognostic factor for older patients. The surgical approach does not significantly impact prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Editorial Material
Cell Biology
Neil P. Blackledge, Robert J. Klose
Summary: The Polycomb repressive system regulates gene expression and development through chromatin. The study by Cohen and colleagues in Genes & Development demonstrates that cooperation between PRC1 and PRC2 enables stable repression of non-epidermal transcription factors, preventing compromise of epidermal cell identity and disruption of normal skin development.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Idan Cohen, Carmit Bar, Hequn Liu, Victor J. Valdes, Dejian Zhao, Phillip M. Galbo, Jose M. Silva, Haruhiko Koseki, Deyo Zheng, Elena Ezhkova
Summary: This study on epidermal development revealed a functional redundancy between Polycomb complex 1 and PRC2, highlighting their important roles in maintaining lineage identity and gene suppression.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Maksim Erokhin, Olga Chetverina, Balazs Gyorffy, Victor V. Tatarskiy, Vladic Mogila, Alexander A. Shtil, Igor B. Roninson, Jerome Moreaux, Pavel Georgiev, Giacomo Cavalli, Darya Chetverina
Summary: PRC2 is a complex involved in transcriptional repression through histone methylation, with dysregulation linked to tumor development. This study analyzed clinical correlations of PRC2 subunit genes in tumor samples, identifying cancer types responsive to PRC2 inhibition and potential sensitivity markers for PRC2-targeting drugs.
Article
Oncology
Eshini Panditharatna, Joana G. Marques, Tingjian Wang, Maria C. Trissal, Ilon Liu, Li Jiang, Alexander Beck, Andrew Groves, Neekesh Dharia, Deyao Li, Samantha E. Hoffman, Guillaume Kugener, McKenzie L. Shaw, Hafsa M. Mire, Olivia A. Hack, Joshua M. Dempster, Caleb Lareau, Lingling Dai, Logan H. Sigua, Michael A. Quezada, Ann-Catherine J. Stanton, Meghan Wyatt, Zohra Kalani, Amy Goodale, Francisca Vazquez, Federica Piccioni, John G. Doench, David E. Root, Jamie N. Anastas, Kristen L. Jones, Amy Saur Conway, Sylwia Stopka, Michael S. Regan, Yu Liang, Hyuk-Soo Seo, Kijun Song, Puspalata Bashyal, William P. Jerome, Nathan D. Mathewson, Sirano Dhe-Paganon, Mario L. Suva, Angel M. Carcaboso, Cinzia Lavarino, Jaume Mora, Quang-De Nguyen, Keith L. Ligon, Yang Shi, Sameer Agnihotri, Nathalie Y. R. Agar, Kimberly Stegmaier, Charles D. Stiles, Michelle Monje, Todd R. Golub, Jun Qi, Mariella G. Filbin
Summary: This article introduces a new treatment strategy for H3K27M gliomas by inhibiting the BAF complex, which promotes differentiation and improves survival in patients.
Article
Oncology
Liang Zhang, Cody L. Nesvick, Charlie A. Day, Jonghoon Choi, Victor M. Lu, Timothy Peterson, Erica A. Power, Jacob B. Anderson, Feda H. Hamdan, Paul A. Decker, Renae Simons, John P. Welby, Ruby Siada, Jizhi Ge, Tatiana Kaptzan, Steven A. Johnsen, Edward H. Hinchcliffe, David J. Daniels
Summary: The study identified STAT3 as a biologically relevant therapeutic target in H3K27M-mutant DMG. STAT3 inhibitors demonstrated robust cytotoxic activity in vitro, and inhibition of STAT3 partially restored expression of the lost polycomb repressive mark H3K27me3 in H3K27M-mutant DMG.
Article
Neurosciences
Xuan Gong, Shuwen Kuang, Dongfeng Deng, Jun Wu, Longbo Zhang, Chao Liu
Summary: This study aimed to investigate the clinicopathological characteristics and identify prognostic factors of H3K27M-mutant diffuse midline glioma (DMG) in pediatric and adult patients. Significant differences were found in clinicopathological characteristics and prognostic factors between children and adults, suggesting the need for further clinical and molecular stratification based on age.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Sasithorn Wanna-Udom, Minoru Terashima, Kusuma Suphakhong, Akihiko Ishimura, Takahisa Takino, Takeshi Suzuki
Summary: The study revealed that KDM2B knockdown inhibits cell transition, enhances cell migration and invasion, while KDM2B overexpression influences the expression of multiple epithelial marker genes and enhances TGF-beta effects during EMT. Mechanistic investigations further showed that KDM2B mediates gene repression in EMT through histone H2A monoubiquitination as part of the PRC1 complex.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Biology
Hua Yan, Shadi Jafari, Gregory Pask, Xiaofan Zhou, Danny Reinberg, Claude Desplan
JOURNAL OF EXPERIMENTAL BIOLOGY
(2020)
Article
Clinical Neurology
Eleanor Drummond, Geoffrey Pires, Claire MacMurray, Manor Askenazi, Shruti Nayak, Marie Bourdon, Jiri Safar, Beatrix Ueberheide, Thomas Wisniewski
Article
Biochemistry & Molecular Biology
Samson M. Jolly, Ildar Gainetdinov, Karina Jouravleva, Han Zhang, Lara Strittmatter, Shannon M. Bailey, Gregory M. Hendricks, Avantika Dhabaria, Beatrix Ueberheide, Phillip D. Zamore
Article
Biology
Russell J. Ledet, Sophie E. Ruff, Yu Wang, Shruti Nayak, Jeffrey A. Schneider, Beatrix Ueberheide, Susan K. Logan, Michael J. Garabedian
Summary: Through a chemical genetics screen and phospho-proteomics, Ledet and Ruff et al identify substrates of the oncogenic kinase PIM1 in prostate cancer cells. They find that NDRG1 protein is destabilized by PIM1-mediated phosphorylation to reduce its metastasis suppressor function. These findings shed light on the role of PIM1 in prostate cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Marianne Strazza, Kieran Adam, Shalom Lerrer, Johanna Straube, Sabina Sandigursky, Beatrix Ueberheide, Adam Mor
Summary: PD-1 is a critical therapeutic target in cancer immunotherapy, with SHP2 playing a key role in its downstream signaling. Research has found that SHP2 specifically dephosphorylates ITK, which is associated with PD-1 inhibitory cellular functions. ITK may be a unique target in this pathway, and combining ITK inhibitors with PD-1 blockade may improve cancer treatment outcomes.
Article
Oncology
Tanaya Lahiri, Lara Brambilla, Joshua Andrade, Manor Askenazi, Beatrix Ueberheide, David E. Levy
Summary: Mitochondrial STAT3 regulates complex I dehydrogenase activity, impacting NAD+ regeneration, thus indirectly controlling antioxidant gene expression to promote proliferation and migration in triple-negative breast cancer cells.
MOLECULAR ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Daniel Grau, Yixiao Zhang, Chul-Hwan Lee, Marco Valencia-Sanchez, Jenny Zhang, Miao Wang, Marlene Holder, Vladimir Svetlov, Dongyan Tan, Evgeny Nudler, Danny Reinberg, Thomas Walz, Karim-Jean Armache
Summary: Polycomb Repressive Complex 2 (PRC2) regulates gene silencing through the selective incorporation of catalytic subunits EZH1 or EZH2, with the EZH1-containing PRC2 dimer showing significant conformational changes when bound to a nucleosome.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Dominique F. Leitner, James D. Mills, Geoffrey Pires, Arline Faustin, Eleanor Drummond, Evgeny Kanshin, Shruti Nayak, Manor Askenazi, Chloe Verducci, Bei Jun Chen, Michael Janitz, Jasper J. Anink, Johannes C. Baayen, Sander Idema, Erwin A. van Vliet, Sasha Devore, Daniel Friedman, Beate Diehl, Catherine Scott, Roland Thijs, Thomas Wisniewski, Beatrix Ueberheide, Maria Thom, Eleonora Aronica, Orrin Devinsky
Summary: The proteomic and transcriptomic analyses showed no differences between SUDEP patients and non-SUDEP epilepsy patients in hippocampus and cortex, suggesting diverse epilepsy syndromes and comorbid conditions in SUDEP. Further studies with larger cohorts and different epilepsy syndromes may reveal the molecular mechanisms underlying SUDEP.
Article
Multidisciplinary Sciences
Elijah L. Mena, Callie J. Donahue, Laura Pontano Vaites, Jie Li, Gergely Rona, Colin O'Leary, Luca Lignitto, Bearach Miwatani-Minter, Joao A. Paulo, Avantika Dhabaria, Beatrix Ueberheide, Steven P. Gygi, Michele Pagano, J. Wade Harper, Robert A. Davey, Stephen J. Elledge
Summary: The study found an interaction between ORF10 and CRL2ZYG11B but no evidence that ORF10 is functioning to inhibit or hijack CRL2ZYG11B.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Madeleine R. Miles, John Seo, Min Jiang, Zachary T. Wilson, Janay Little, Jon Hao, Joshua Andrade, Beatrix Ueberheide, Gea-Ny Tseng
Summary: High-throughput experiments suggest that around 20% of human proteins may undergo S-palmitoylation, with proteins in the cardiac palmitoylome mainly involved in cell-cell junctions and mitochondrial enzyme organization. The cardiac palmitoylome is uniquely enriched in proteins related to the organization of t-tubules, costameres, and intercalated discs.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Medicine, Research & Experimental
Adrianna C. Shembel, Evgeny Kanshin, Beatrix Ueberheide, Aaron M. Johnson
Summary: This study compared global protein expression in laryngeal and hindlimb muscles, finding over 1,000 proteins in common across age groups. Age-related differences were observed in 107 proteins in hindlimb muscle and 19 proteins in laryngeal muscle. Differences in protein expression may relate to immune responses, stress redox, and RNA repair.
Article
Multidisciplinary Sciences
Heyi Yang, Erin R. Butler, Samantha A. Monier, Jennifer Teubl, David Fenyo, Beatrix Ueberheide, Donald Siegel
Summary: Proteogenomics is a method for species identification by analyzing the proteome of an unknown organism, even when it is partially degraded. The identification is based on detecting species-specific peptides, which can be challenging due to current limitations in mass spectrometry and algorithm interpretation errors.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jia-Ray Yu, Gary LeRoy, Devin Bready, Joshua D. Frenster, Ricardo Saldana-Meyer, Ying Jin, Nicolas Descostes, James M. Stafford, Dimitris G. Placantonakis, Danny Reinberg
Summary: The study identified that H3K36me2 promotes tumorigenesis in H3K27M-DIPG by affecting the writing activity of NSD1 and NSD2, as well as the reading factors LEDGF and HDGF2. Loss of NSD1/2 impedes cellular proliferation and tumorigenesis.
Review
Biochemistry & Molecular Biology
Soo Hyun Lee, Yingying Li, Hanbyeol Kim, Seounghyun Eum, Kyumin Park, Chul-Hwan Lee
Summary: PRC2/EZH1 and PRC2/EZH2 have distinct functions in early and late developmental stages, and their dysregulation is associated with cancer and developmental diseases. Understanding the differences in their expression patterns, histone methyltransferase activity, and DNA/nucleosome binding activity can provide insights into their roles in heterochromatin formation.
Article
Clinical Neurology
Geoffrey Pires, Dominique Leitner, Eleanor Drummond, Evgeny Kanshin, Shruti Nayak, Manor Askenazi, Arline Faustin, Daniel Friedman, Ludovic Debure, Beatrix Ueberheide, Thomas Wisniewski, Orrin Devinsky
Summary: Epilepsy is a common neurological disorder affecting over 70 million people worldwide and often characterized by high pharmaco-resistance and diverse comorbidities. Proteomic analysis revealed significant protein expression differences in epilepsy cases compared to controls, with G-protein subunit beta 1 (GNB1) showing consistent decrease across brain regions, emphasizing its potential role in epilepsy pathogenesis and suggesting novel therapeutic strategies.
BRAIN COMMUNICATIONS
(2021)