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https://www.readbyqxmd.com/read/28529595/rnf2-knockdown-reduces-cell-viability-and-promotes-cell-cycle-arrest-in-gastric-cancer-cells
#1
Jingfang Zhang, Zhenni Sun, Yafei Han, Ruyong Yao, Lu Yue, Yan Xu, Jisheng Zhang
Rnf2 is a fundamental component of the polycomb repressive complex 1and acts as the really interesting new gene finger E3 ligase, which is responsible for histone 2A modification. Previous studies have shown that the ring finger protein 2 (Rnf2) is overexpressed in various types of tumor and has a close association with tumor development. However, few studies have been carried out into the expression and biological function of Rnf2 in gastric cancer cells. The present study measured the expression of Rnf2 in gastric cancer cells and normal epithelial gastric cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#2
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512399/protein-s-negatively-regulates-neural-stem-cell-self-renewal-through-bmi-1-signaling
#3
Katya Zelentsova-Levytskyi, Ziv Talmi, Ghada Abboud-Jarrous, Tal Capucha, Tamar Sapir, Tal Burstyn-Cohen
Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expression of Protein S (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC quiescence and neuronal differentiation. Here, we investigate the effect of PROS1 on NSPC self-renewal and show that genetic ablation of Pros1 in neural progenitors increased NSPC self-renewal by 50%...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#4
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28505103/neuronal-migration-and-auts2-syndrome
#5
REVIEW
Kei Hori, Mikio Hoshino
Neuronal migration is one of the pivotal steps to form a functional brain, and disorganization of this process is believed to underlie the pathology of psychiatric disorders including schizophrenia, autism spectrum disorders (ASD) and epilepsy. However, it is not clear how abnormal neuronal migration causes mental dysfunction. Recently, a key gene for various psychiatric diseases, the Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal migration, which gives new insight into understanding this question...
May 14, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28500307/alox5-exhibits-anti-tumor-and-drug-sensitizing-effects-in-mll-rearranged-leukemia
#6
Yungui Wang, Jennifer R Skibbe, Chao Hu, Lei Dong, Kyle Ferchen, Rui Su, Chenying Li, Hao Huang, Hengyou Weng, Huilin Huang, Xi Qin, Jie Jin, Jianjun Chen, Xi Jiang
MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediated by Polycomb repressive complex 2 (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500253/linc00341-exerts-an-anti-inflammatory-effect-on-endothelial-cells-by-repressing-vcam1
#7
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Y-J Shyy, Shu Chien
The long non-coding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28498016/accelerated-vernalization-response-by-an-altered-phd-finger-protein-in-arabidopsis
#8
Dong-Hwan Kim, Sibum Sung
Vernalization is a response to the winter cold to acquire the competence to flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein that binds to modified histones in vitro. VIN3 is induced by long-term cold and is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger domain of VIN3 in vitro and results in an accelerated vernalization response in vivo...
May 12, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28491069/characterization-of-the-polycomb-group-mark-h3k27me3-in-unicellular-algae
#9
Pawel Mikulski, Olga Komarynets, Fabio Fachinelli, Andreas P M Weber, Daniel Schubert
Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and modus operandi in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#10
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28485167/expression-and-clinicopathological-significance-of-mel-18-and-bmi-1-in-oesophageal-squamous-cell-carcinoma
#11
H J Ji, M Cao, K L Ren, N B Sun, B Xu, X T Chang, W Wang, Q Zang, Z M Jiang
The Polycomb group (PcG) genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. PcG expression plays an important role in oncogenesis of several types of human cancer. Mel-18 and Bmi-1 are key PcG proteins. Studies have shown that Mel-18 is a potential tumour suppression and Bmi-1 is overexpressed in several human malignancies. However, the roles of Mel-18 and Bmi-1 in oesophageal squamous cell carcinoma (ESCC) are still unclear. In this study, we analysed the expression levels of Mel-18 and Bmi-1 in 89 oesophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting and quantitative real-time PCR (QRT-PCR) analyses...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28483764/polycomb-repressive-complexes-in-hematological-malignancies
#12
Atsushi Iwama
The deregulation of polycomb repressive complexes (PRC) has been reported in a number of hematological malignancies. These complexes exert oncogenic or tumor-suppressive functions depending on the tumor types. These findings have revolutionized our understanding of the pathophysiology of hematological malignancies and the impact of deregulated epigenomes in tumor development and progression. The therapeutic targeting of PRC is currently attracting increasing attention and being extensively examined in clinical studies, leading to new therapeutic strategies that may improve the outcomes of patients with hematological malignancies...
May 8, 2017: Blood
https://www.readbyqxmd.com/read/28483375/mechanisms-regulating-prc2-recruitment-and-enzymatic-activity
#13
REVIEW
Daniel Holoch, Raphaël Margueron
Polycomb repressive complex 2 (PRC2) and its histone H3 lysine-27 methylation activity are crucial for multicellular development by virtue of their role in maintaining transcriptional repression patterns. The recruitment and enzymatic activity of PRC2 are controlled by a series of intricate mechanisms whose molecular details have been emerging at a rapid pace. Recent studies have uncovered intriguing modes of PRC2 regulation by facultative PRC2 subunits, PRC1, and specific features of the chromatin environment...
May 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28475876/keep-them-close-prc2-poises-enhancer-promoter-interactions-at-anterior-neuronal-genes
#14
Giulia Caglio, Elena Torlai Triglia, Ana Pombo
Enhancers exist in different epigenetic states: active, primed, or poised. However, it is not yet understood how the different enhancer states influence gene activation. In this issue of Cell Stem Cell, Cruz-Molina et al. (2017) unravel how poised enhancers activate anterior neural genes and the role of Polycomb proteins in enhancer-promoter contacts.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28468635/prc2-represses-transcribed-genes-on-the-imprinted-inactive-x-chromosome-in-mice
#15
Emily Maclary, Michael Hinten, Clair Harris, Shriya Sethuraman, Srimonta Gayen, Sundeep Kalantry
BACKGROUND: Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which marks many transcriptionally silent genes throughout the mammalian genome. Although H3K27me3 is associated with silenced gene expression broadly, it remains unclear why some but not other PRC2 target genes require PRC2 and H3K27me3 for silencing. RESULTS: Here we define the transcriptional and chromatin features that predict which PRC2 target genes require PRC2/H3K27me3 for silencing by interrogating imprinted mouse X-chromosome inactivation...
May 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#16
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#17
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
April 29, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28460453/cbx7-is-a-glioma-prognostic-marker-and-induces-g1-s-arrest-via-the-silencing-of-ccne1
#18
Tianfu Yu, Youzhi Wu, Qi Hu, Junxia Zhang, Er Nie, Weining Wu, Xiefeng Wang, Yingyi Wang, Ning Liu
Chromobox homolog 7 (CBX7) cooperates with other polycomb group (PcG) proteins to maintain target genes in a silenced state. However, the precise role of CBX7 in tumor progression is still controversial. We found that the expression of CBX7 in four public databases was significantly lower in high grade glioma (HGG). The reduced expression of CBX7 correlated with poor outcome in HGG patients. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459462/genome-wide-dna-methylation-profiling-reveals-cancer-associated-changes-within-early-colonic-neoplasia
#19
M P Hanley, M A Hahn, A X Li, X Wu, J Lin, J Wang, A H Choi, Z Ouyang, Y Fong, G P Pfeifer, T J Devers, D W Rosenberg
Colorectal cancer (CRC) is characterized by genome-wide alterations to DNA methylation that influence gene expression and genomic stability. Less is known about the extent to which methylation is disrupted in the earliest stages of CRC development. In this study, we have combined laser-capture microdissection with reduced representation bisulfite sequencing to identify cancer-associated DNA methylation changes in human aberrant crypt foci (ACF), the earliest putative precursor to CRC. Using this approach, methylation profiles have been generated for 10 KRAS-mutant ACF and 10 CRCs harboring a KRAS mutation, as well as matched samples of normal mucosa...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28455403/concerted-divergence-after-gene-duplication-in-polycomb-repressor-complexes
#20
Yichun Qiu, Shao-Lun Liu, Keith L Adams
Duplicated genes are a major contributor to genome evolution and phenotypic novelty. There are multiple possible evolutionary fates of duplicated genes. Here we provide an example of concerted divergence of simultaneously duplicated genes whose products function in the same complex. We studied PRC2 (Polycomb Repressive Complex 2) in Brassicaceae. The VRN-PRC2 complex contains VRN2 and SWN, and both genes were duplicated during a whole genome duplication to generate FIS2 and MEA which function in the Brassicaceae-specific FIS-PRC2 complex that regulates seed development...
April 28, 2017: Plant Physiology
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