keyword
https://read.qxmd.com/read/37499944/polycomb-proteins-translate-histone-methylation-to-chromatin-folding
#21
JOURNAL ARTICLE
Ludvig Lizana, Negar Nahali, Yuri B Schwartz
Epigenetic repression often involves covalent histone modifications. Yet, how the presence of a histone mark translates into changes in chromatin structure that ultimately benefit the repression is largely unclear. Polycomb group proteins comprise a family of evolutionarily conserved epigenetic repressors. They act as multi-subunit complexes one of which tri-methylates histone H3 at Lysine 27 (H3K27). Here we describe a novel Monte Carlo - Molecular Dynamics simulation framework, which we employed to discover that stochastic interaction of the Polycomb Repressive Complex 1 (PRC1) with tri-methylated H3K27 is sufficient to fold the methylated chromatin...
July 25, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37332606/targeting-the-prc2-dependent-epigenetic-program-alleviates-urinary-tract-infections
#22
JOURNAL ARTICLE
Chunming Guo, Mingyi Zhao, Xinbing Sui, Zarine Balsara, Songhui Zhai, Michael Ahdoot, Yingsheng Zhang, Christa M Lam, Ping Zhu, Xue Li
Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)-a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway...
June 16, 2023: IScience
https://read.qxmd.com/read/37243607/novel-chromobox-2-inhibitory-peptide-decreases-tumor-progression
#23
JOURNAL ARTICLE
Lindsay W Brubaker, Donald S Backos, Vu T Nguyen, Philip Reigan, Tomomi M Yamamoto, Elizabeth R Woodruff, Ritsuko Iwanaga, Michael F Wempe, Vijay Kumar, Christianne Persenaire, Zachary L Watson, Benjamin G Bitler
BACKGROUND: The Polycomb Repressor Complex 1 (PRC1) is an epigenetic regulator of differentiation and development, consisting of multiple subunits including RING1, BMI1, and Chromobox. The composition of PRC1 dictates its function and aberrant expression of specific subunits contributes to several diseases including cancer. Specifically, the reader protein Chromobox2 (CBX2) recognizes the repressive modifications including histone H3 lysine 27 tri-methylation (H3K27me3) and H3 lysine 9 dimethylation (H3K9me2)...
May 27, 2023: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/37212989/co-immunoprecipitation-co-ip-in-mammalian-cells
#24
JOURNAL ARTICLE
Federica Lo Sardo
The cell is a fantastic place where molecules dynamically move through the various cellular structures and compartments and meet each other, either transiently or in more stable complexes. These complexes have always a specific biological function; thus, it is important to identify and characterize the interaction between molecules, either DNA/RNA, DNA/DNA, protein/DNA, protein/protein, and so on. polycomb group proteins (PcG proteins) are epigenetic repressors involved in important physiologic processes as development and differentiation...
2023: Methods in Molecular Biology
https://read.qxmd.com/read/37207700/ezh2-can-be-used-as-a-therapeutic-agent-for-inhibiting-endothelial-dysfunction
#25
REVIEW
Li Sun, Xuefang Li, Hui Luo, Huige Guo, Jie Zhang, Zhigang Chen, Fei Lin, Guoan Zhao
Enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressor complex 2 and plays important roles in endothelial cell homeostasis. EZH2 functionally methylates lysine 27 of histone H3 and represses gene expression through chromatin compaction. EZH2 mediates the effects of environmental stimuli by regulating endothelial functions, such as angiogenesis, endothelial barrier integrity, inflammatory signaling, and endothelial mesenchymal transition. Numerous studies have been conducted to determine the significance of EZH2 in endothelial function...
May 17, 2023: Biochemical Pharmacology
https://read.qxmd.com/read/37132544/bmi1-is-required-for-melanocyte-stem-cell-maintenance-and-hair-pigmentation
#26
JOURNAL ARTICLE
Molly M Wilson, Paul S Danielian, Griffin Salus, Roberta Ferretti, Charles A Whittaker, Jacqueline A Lees
The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16Ink4a and p19Arf . However, in cutaneous melanoma, BMI1 drives epithelial-mesenchymal transition programs, and thus metastasis, while having little impact on proliferation or primary tumor growth. This raised questions about the requirement and role for BMI1 in melanocyte stem cell (McSC) biology...
May 3, 2023: Pigment Cell & Melanoma Research
https://read.qxmd.com/read/37024684/dynamic-antagonism-between-key-repressive-pathways-maintains-the-placental-epigenome
#27
JOURNAL ARTICLE
Raha Weigert, Sara Hetzel, Nina Bailly, Chuck Haggerty, Ibrahim A Ilik, Philip Yuk Kwong Yung, Carmen Navarro, Adriano Bolondi, Abhishek Sampath Kumar, Chiara Anania, Björn Brändl, David Meierhofer, Darío G Lupiáñez, Franz-Josef Müller, Tugce Aktas, Simon J Elsässer, Helene Kretzmer, Zachary D Smith, Alexander Meissner
DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains. Here, to better understand this unusual landscape's molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse trophoblast stem cells...
April 2023: Nature Cell Biology
https://read.qxmd.com/read/37003503/macrotubule-associated-protein-map1lc3c-regulates-lysosomal-exocytosis-and-induces-zinc-reprogramming-in-renal-cancer-cells
#28
JOURNAL ARTICLE
Rita Verma, Parul Aggarwal, Megan E Bischoff, James Reigle, Dina Secic, Collin Wetzel, Katherine VandenHeuvel, Jacek Biesiada, Birgit Ehmer, Julio A Landero Figueroa, David R Plas, Mario Medvedovic, Jarek Meller, Maria F Czyzyk-Krzeska
Microtubule Associated Protein 1 Light Chain 3 Gamma (MAP1LC3C or LC3C) is a member of the microtubule associated family of proteins that are essential in the formation of autophagosomes and lysosomal degradation of cargo. LC3C has tumor suppressing activity and its expression is dependent on kidney cancer tumor suppressors, such as von Hippel-Lindau protein (VHL) and folliculin (FLCN). Recently We demonstrated that LC3C autophagy is regulated by noncanonical upstream regulatory complexes and targets for degradation postdivision midbody rings associated with cancer cells stemness...
March 30, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/36980273/the-linc-complex-inhibits-excessive-chromatin-repression
#29
JOURNAL ARTICLE
Daria Amiad Pavlov, C P Unnikannan, Dana Lorber, Gaurav Bajpai, Tsviya Olender, Elizabeth Stoops, Adriana Reuveny, Samuel Safran, Talila Volk
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex transduces nuclear mechanical inputs suggested to control chromatin organization and gene expression; however, the underlying mechanism is currently unclear. We show here that the LINC complex is needed to minimize chromatin repression in muscle tissue, where the nuclei are exposed to significant mechanical inputs during muscle contraction. To this end, the genomic binding profiles of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex...
March 18, 2023: Cells
https://read.qxmd.com/read/36973442/drug-addiction-unveils-a-repressive-methylation-ceiling-in-ezh2-mutant-lymphoma
#30
JOURNAL ARTICLE
Hui Si Kwok, Allyson M Freedy, Allison P Siegenfeld, Julia W Morriss, Amanda L Waterbury, Stephen M Kissler, Brian B Liau
Drug addiction, a phenomenon where cancer cells paradoxically depend on continuous drug treatment for survival, has uncovered cell signaling mechanisms and cancer codependencies. Here we discover mutations that confer drug addiction to inhibitors of the transcriptional repressor polycomb repressive complex 2 (PRC2) in diffuse large B-cell lymphoma. Drug addiction is mediated by hypermorphic mutations in the CXC domain of the catalytic subunit EZH2, which maintain H3K27me3 levels even in the presence of PRC2 inhibitors...
March 27, 2023: Nature Chemical Biology
https://read.qxmd.com/read/36941433/loss-of-h3k9-trimethylation-alters-chromosome-compaction-and-transcription-factor-retention-during-mitosis
#31
JOURNAL ARTICLE
Dounia Djeghloul, Andrew Dimond, Sherry Cheriyamkunnel, Holger Kramer, Bhavik Patel, Karen Brown, Alex Montoya, Chad Whilding, Yi-Fang Wang, Matthias E Futschik, Nicolas Veland, Thomas Montavon, Thomas Jenuwein, Matthias Merkenschlager, Amanda G Fisher
Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we show that enzymes that catalyze H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly, however, mutants lacking histone 3 lysine 9 trimethylation (H3K9me3) have unusually small and compact mitotic chromosomes associated with increased histone H3 phospho Ser10 (H3S10ph) and H3K27me3 levels...
March 20, 2023: Nature Structural & Molecular Biology
https://read.qxmd.com/read/36893455/molecular-basis-of-polycomb-group-protein-mediated-fetal-hemoglobin-repression
#32
JOURNAL ARTICLE
Kunhua Qin, Xianjiang Lan, Peng Huang, Megan S Saari, Eugene Khandros, Cheryl A Keller, Belinda M Giardine, Osheiza Abdulmalik, Junwei Shi, Ross C Hardison, Gerd A Blobel
The fetal (HbF)-to-adult (HbA) hemoglobin switch is a paradigm for developmental gene expression control with relevance to sickle cell disease and b-thalassemia. Polycomb repressive complex (PRC) proteins regulate this switch, and an inhibitor of PRC2 has entered a clinical trial for fetal hemoglobin activation. Yet, how PRC complexes function in this process, their target genes, and relevant subunit composition are unknown. Here, we identified the PRC1 subunit BMI1 as a novel HbF repressor. We uncovered the RNA binding proteins LIN28B, IGF2BP1, and IGF2BP3 as direct BMI1 targets and demonstrate that they account for the entirety of BMI1's effects on HbF regulation...
March 9, 2023: Blood
https://read.qxmd.com/read/36845425/the-role-of-histone-methyltransferases-in-neurocognitive-disorders-associated-with-brain-size-abnormalities
#33
REVIEW
Foster D Ritchie, Sofia B Lizarraga
Brain size is controlled by several factors during neuronal development, including neural progenitor proliferation, neuronal arborization, gliogenesis, cell death, and synaptogenesis. Multiple neurodevelopmental disorders have co-morbid brain size abnormalities, such as microcephaly and macrocephaly. Mutations in histone methyltransferases that modify histone H3 on Lysine 36 and Lysine 4 (H3K36 and H3K4) have been identified in neurodevelopmental disorders involving both microcephaly and macrocephaly. H3K36 and H3K4 methylation are both associated with transcriptional activation and are proposed to sterically hinder the repressive activity of the Polycomb Repressor Complex 2 (PRC2)...
2023: Frontiers in Neuroscience
https://read.qxmd.com/read/36808292/histone-modification-landscape-and-the-key-significance-of-h3k27me3-in-myocardial-ischaemia-reperfusion-injury
#34
JOURNAL ARTICLE
Le Ni, Bowen Lin, Yanping Zhang, Lingjie Hu, Jianghua Lin, Fengmei Fu, Meiting Shen, Can Li, Lei Chen, Jian Yang, Dan Shi, Yi-Han Chen
Histone modifications play crucial roles in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury. However, a genome-wide map of histone modifications and the underlying epigenetic signatures in myocardial I/R injury have not been established. Here, we integrated transcriptome and epigenome of histone modifications to characterize epigenetic signatures after I/R injury. Disease-specific histone mark alterations were mainly found in H3K27me3-, H3K27ac-, and H3K4me1-marked regions 24 and 48 h after I/R...
February 13, 2023: Science China. Life Sciences
https://read.qxmd.com/read/36765545/synovial-sarcoma-preclinical-modeling-integrating-transgenic-mouse-models-and-patient-derived-models-for-translational-research
#35
REVIEW
Lorena Landuzzi, Francesca Ruzzi, Pier-Luigi Lollini, Katia Scotlandi
Synovial sarcomas (SyS) are rare malignant tumors predominantly affecting children, adolescents, and young adults. The genetic hallmark of SyS is the t(X;18) translocation encoding the SS18-SSX fusion gene. The fusion protein interacts with both the BAF enhancer and polycomb repressor complexes, and either activates or represses target gene transcription, resulting in genome-wide epigenetic perturbations and altered gene expression. Several experimental in in vivo models, including conditional transgenic mouse models expressing the SS18-SSX fusion protein and spontaneously developing SyS, are available...
January 18, 2023: Cancers
https://read.qxmd.com/read/36751888/polycomb-protein-rybp-activates-transcription-factor-plagl1-during-in-vitro-cardiac-differentiation-of-mouse-embryonic-stem-cells
#36
JOURNAL ARTICLE
Surya Henry, Lilla Kokity, Melinda Katalin Pirity
RING1 and YY1 binding protein (RYBP) is primarily known to function as a repressor being a core component of the non-canonical polycomb repressive complexes 1 (ncPRC1s). However, several ncPRC1-independent functions of RYBP have also been described. We previously reported that RYBP is essential for mouse embryonic development and that Rybp null mutant embryonic stem cells cannot form contractile cardiomyocytes (CMCs) in vitro . We also showed that PLAGL1, a cardiac transcription factor, which is often mutated in congenital heart diseases (CHDs), is not expressed in Rybp -null mutant CMCs...
February 2023: Open Biology
https://read.qxmd.com/read/36738766/histone-h2a-deubiquitinases-in-the-transcriptional-programs-of-development-and-hematopoiesis-a-consolidated-analysis
#37
JOURNAL ARTICLE
HanChen Wang, David Langlais, Anastasia Nijnik
Monoubiquitinated lysine 119 of histone H2A (H2AK119ub) is a highly abundant epigenetic mark, associated with gene repression and deposited on chromatin by the polycomb repressor complex 1 (PRC1), which is an essential regulator of diverse transcriptional programs in mammalian development and tissue homeostasis. While multiple deubiquitinases (DUBs) with catalytic activity for H2AK119ub (H2A-DUBs) have been identified, we lack systematic analyses of their roles and cross-talk in transcriptional regulation. Here, we address H2A-DUB functions in epigenetic regulation of mammalian development and tissue maintenance by conducting a meta-analysis of 248 genomics datasets from 32 independent studies, focusing on the mouse model and covering embryonic stem cells (ESCs), hematopoietic, and immune cell lineages...
February 2, 2023: International Journal of Biochemistry & Cell Biology
https://read.qxmd.com/read/36718085/beyond-expression-role-of-phosphorylated-residues-of-ezh2-in-lineage-plasticity-in-prostate-cancer
#38
JOURNAL ARTICLE
Shaghayegh Nouruzi, Nakisa Tabrizian, Amina Zoubeidi
Despite the development of effective targeted therapies and a significant understanding of carcinogenesis and cancer progression, treatment resistance is a major obstacle in achieving durable long-term control in many types of cancers. Emerging evidence supports that non-genetic mechanisms could play an underappreciated role in therapy resistance. These mechanisms include phenotypic plasticity, which is recognized as one of the hallmarks of cancer and translates to epigenetic and transcriptional control of gene expression...
January 30, 2023: Endocrinology
https://read.qxmd.com/read/36672374/ezh2-an-accomplice-of-gastric-cancer
#39
REVIEW
Wuhan Yu, Ning Liu, Xiaogang Song, Lang Chen, Mancai Wang, Guohui Xiao, Tengfei Li, Zheyuan Wang, Youcheng Zhang
Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms...
January 9, 2023: Cancers
https://read.qxmd.com/read/36621979/loss-of-cbx2-causes-genomic-instability-and-wnt-activation-in-high-grade-serous-ovarian-carcinoma-cells
#40
JOURNAL ARTICLE
Yujia Ma, Lin Liu, Zheng Wei, Mengna Zhu, Lin Huang, Shan Wang, Xiaoqing Yi, Feiquan Ying, Simei Zhao, Jing Cai, Zehua Wang, Si Sun
High grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis-associated PRC1 components were identified through data-mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3...
January 9, 2023: Molecular Carcinogenesis
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