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https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#1
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27892467/jarid2-binds-mono-ubiquitylated-h2a-lysine-119-to-mediate-crosstalk-between-polycomb-complexes-prc1-and-prc2
#2
Sarah Cooper, Anne Grijzenhout, Elizabeth Underwood, Katia Ancelin, Tianyi Zhang, Tatyana B Nesterova, Burcu Anil-Kirmizitas, Andrew Bassett, Susanne M Kooistra, Karl Agger, Kristian Helin, Edith Heard, Neil Brockdorff
The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881472/an-unexpected-regulatory-cascade-governs-a-core-function-of-the-drosophila-prc1-chromatin-protein-su-z-2
#3
Son C Nguyen, Stephanie Yu, Elaine Oberlick, Chao-Ting Wu
Polycomb group (PcG) proteins are major chromatin-bound factors that can read and modify chromatin states to maintain gene silencing throughout development. Here we focus on a close homolog of the PcG protein Posterior sex combs in order to better understand how these proteins affect regulation. This homolog, called Suppressor 2 of zeste, or Su(z)2 is comprised of two regions: the N-terminal "homology region" (HR), which serves as a hub for protein interactions, and the C-terminal region (CTR), which is believed to harbor the core activity of compacting chromatin...
November 23, 2016: Genetics
https://www.readbyqxmd.com/read/27879390/phosphorylation-of-map65-1-by-arabidopsis-aurora-kinases-is-required-for-efficient-cell-cycle-progression
#4
Joanna Boruc, Annika Weimer, Virginie Stoppin-Mellet, Evelien Mylle, Ken Kosetsu, Cesyen Cedeno, Michel Jaquinod, Maria Njo, Liesbeth De Milde, Peter Tompa, Nathalie Gonzalez, Dirk Inze, Tom Beeckman, Marylin Vantard, Daniel van Damme
Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The α Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The β Aurora (Aurora3) localizes to centromeres and likely functions in chromosome separation. In contrast to the wealth of data available on the role of Aurora in other kingdoms, knowledge on their function in plants is merely emerging. This is exemplified by the fact that only histone H3 and the plant homologue of TPX2 have been identified as Aurora substrates in plants...
November 22, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27864346/cbx4-suppresses-metastasis-via-recruitment-of-hdac3-to-the-runx2-promoter-in-colorectal-carcinoma
#5
Xin Wang, Liping Li, Yuanzhong Wu, Ruhua Zhang, Meifang Zhang, Dan Liao, Gang Wang, Ge Qin, Rui-Hua Xu, Tiebang Kang
Polycomb chromobox (CBX) proteins participate in the polycomb repressive complex (PRC1) that mediates epigenetic gene silencing and endow PRC1 with distinct oncogenic or tumor suppressor functions in a cell type-dependent manner. In this study, we report that inhibition of cell migration, invasion, and metastasis in colorectal carcinoma (CRC) requires CBX4-mediated repression of Runx2, a key transcription factor that promotes CRC metastasis. CBX4 inversely correlated with Runx2 expression in CRC tissues, and the combination of high CBX4 expression and low Runx2 expression significantly correlated with overall survival, more so than either CBX4 or Runx2 expresson alone...
November 18, 2016: Cancer Research
https://www.readbyqxmd.com/read/27856324/mll-af4-binds-directly-to-a-bcl-2-specific-enhancer-and-modulates-h3k27-acetylation
#6
Laura Godfrey, Jon Kerry, Ross Thorne, Emmanouela Repapi, James O J Davies, Marta Tapia, Erica Ballabio, Jim R Hughes, Huimin Geng, Marina Konopleva, Thomas A Milne
Survival rates for children and adults carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in ALL is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we demonstrated that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. Here, we perform a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
November 14, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27843583/nanostring-expression-profiling-identifies-candidate-biomarkers-of-rad001-response-in-metastatic-gastric-cancer
#7
Kakoli Das, Xiu Bin Chan, David Epstein, Bin Tean Teh, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Won Ki Kang, Steve Rozen, Jeeyun Lee, Patrick Tan
BACKGROUND: Gene expression profiling has contributed greatly to cancer research. However, expression-driven biomarker discovery in metastatic gastric cancer (mGC) remains unclear. A gene expression profile predicting RAD001 response in refractory GC was explored in this study. METHODS: Total RNA isolated from 54 tumour specimens from patients with mGC, prior to RAD001 treatment, was analysed via the NanoString nCounter gene expression assay. This assay targeted 477 genes representing 10 different GC-related oncogenic signalling and molecular subtype-specific expression signatures...
2016: ESMO Open
https://www.readbyqxmd.com/read/27837089/the-arabidopsis-polycomb-repressive-complex-1-prc1-components-atbmi1a-b-and-c-impact-gene-networks-throughout-all-stages-of-plant-development
#8
Wiam Merini, Francisco J Romero-Campero, Angeles Gomez-Zambrano, Yue Zhou, Franziska Turck, Myriam Calonje
PcG regulation in Arabidopsis is required to maintain cell differentiation and to allow developmental phase transitions. This is achieved by the activity of three PRC2s and the participation of a yet poorly defined PRC1. Previous results showed that apparent PRC1 components perform discrete roles during plant development, suggesting the existence of PRC1 variants; however, it is not clear in how many processes these components participate. We show that AtBMI1 proteins are required to promote all developmental phase transitions and to control cell proliferation during organ growth and development, expanding their proposed range of action...
November 9, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27835888/motor-activity-of-centromere-associated-protein-e-contributes-to-its-localization-at-the-center-of-the-midbody-to-regulate-cytokinetic-abscission
#9
Akihiro Ohashi, Momoko Ohori, Kenichi Iwai
Accurate control of cytokinesis is critical for genomic stability to complete high-fidelity transmission of genetic material to the next generation. A number of proteins accumulate in the intercellular bridge (midbody) during cytokinesis, and the dynamics of these proteins are temporally and spatially orchestrated to complete the process. In this study, we demonstrated that localization of centromere-associated protein-E (CENP-E) at the midbody is involved in cytokinetic abscission. The motor activity of CENP-E and the C-terminal midbody localization domain, which includes amino acids 2659-2666 (RYFDNSSL), are involved in the anchoring of CENP-E to the center of the midbody...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835578/integrated-bioinformatics-analysis-of-chromatin-regulator-ezh2-in-regulating-mrna-and-lncrna-expression-by-chip-sequencing-and-rna-sequencing
#10
Yuan Li, Mei Luo, Xuejiao Shi, Zhiliang Lu, Shouguo Sun, Jianbing Huang, Zhaoli Chen, Jie He
Enhancer of zeste homolog 2 (EZH2), a dynamic chromatin regulator in cancer, represents a potential therapeutic target showing early signs of promise in clinical trials. EZH2 ChIP sequencing data in 19 cell lines and RNA sequencing data in ten cancer types were downloaded from GEO and TCGA, respectively. Integrated ChIP sequencing analysis and co-expressing analysis were conducted and both mRNA and long noncoding RNA (lncRNA) targets were detected. We detected a median of 4,672 mRNA targets and 4,024 lncRNA targets regulated by EZH2 in 19 cell lines...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27827373/bmi1-regulates-prc1-architecture-and-activity-through-homo-and-hetero-oligomerization
#11
Felicia Gray, Hyo Je Cho, Shirish Shukla, Shihan He, Ashley Harris, Bohdan Boytsov, Łukasz Jaremko, Mariusz Jaremko, Borries Demeler, Elizabeth R Lawlor, Jolanta Grembecka, Tomasz Cierpicki
BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein-protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a β-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27796194/aplp2-rrm2-and-prc1-new-putative-markers-for-the-differential-diagnosis-of-thyroid-follicular-lesions
#12
Esmeralda Castelblanco, Carles Zafon, Javier Maravall, Pilar Gallel, Montserrat Martinez, Ismael Capel, Maria Rosa Bella, Irene Halperin, Jordi Temprana, Carmela Iglesias, Manel Puig-Domingo, Mercedes Robledo, Xavier Matias-Guiu, Didac Mauricio
BACKGROUND: Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions...
November 30, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27793053/epigenetic-regulation-of-cancer-biology-and-anti-tumor-immunity-by-ezh2
#13
Anthos Christofides, Theodoros Karantanos, Kankana Bardhan, Vassiliki A Boussiotis
Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure...
October 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27773671/moz-and-bmi1-act-synergistically-to-maintain-hematopoietic-stem-cells
#14
Bilal N Sheikh, Donald Metcalf, Anne K Voss, Tim Thomas
Chromatin plays a central role in maintaining hematopoietic stem cells and during their stepwise differentiation. Although a large number of histone modifications and chromatin-modifying enzymes have been identified, how these act in concert to produce specific phenotypic outcomes remains to be established. MOZ (KAT6A) is a lysine acetyltransferase and enhances transcription at target gene loci. In contrast, the Polycomb group protein BMI1 (PCGF4) is part of the transcriptionally repressive PRC1 complex. Despite their opposing effects on transcription, MOZ and BMI1 regulate biological systems in a similar manner...
October 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27730210/maintenance-of-leukemic-cell-identity-by-the-activity-of-the-polycomb-complex-prc1-in-mice
#15
Alessandra Rossi, Karin J Ferrari, Andrea Piunti, SriGanesh Jammula, Fulvio Chiacchiera, Luca Mazzarella, Andrea Scelfo, Pier Giuseppe Pelicci, Diego Pasini
Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several fusion proteins induce leukemogenesis by activating Hox gene expression (Hox-activating fusions), others impinge on different pathways that do not involve the activation of Hox genes (non-Hox-activating fusions). It has been postulated that one of the main oncogenic properties of the HOXA9 transcription factor is its ability to control the expression of the p16/p19 tumor suppressor locus (Cdkn2a), thereby compensating Polycomb-mediated repression, which is dispensable for leukemias induced by Hox-activating fusions...
October 2016: Science Advances
https://www.readbyqxmd.com/read/27723458/live-cell-single-molecule-tracking-reveals-co-recognition-of-h3k27me3-and-dna-targets-polycomb-cbx7-prc1-to-chromatin
#16
Chao Yu Zhen, Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Raibatak Das, Marko Kokotovic, Jonathan B Grimm, Luke D Lavis, Jun Lee, Frances J Mejia, Yang Li, Tingting Yao, Xiaojun Ren
The Polycomb PRC1 plays essential roles in development and disease pathogenesis. Targeting of PRC1 to chromatin is thought to be mediated by the Cbx family proteins (Cbx2/4/6/7/8) binding to histone H3 with a K27me3 modification (H3K27me3). Despite this prevailing view, the molecular mechanisms of targeting remain poorly understood. Here, by combining live-cell single-molecule tracking (SMT) and genetic engineering, we reveal that H3K27me3 contributes significantly to the targeting of Cbx7 and Cbx8 to chromatin, but less to Cbx2, Cbx4, and Cbx6...
October 10, 2016: ELife
https://www.readbyqxmd.com/read/27705803/a-high-density-map-for-navigating-the-human-polycomb-complexome
#17
Simon Hauri, Federico Comoglio, Makiko Seimiya, Moritz Gerstung, Timo Glatter, Klaus Hansen, Ruedi Aebersold, Renato Paro, Matthias Gstaiger, Christian Beisel
Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. Our high-density protein interaction network uncovered a diverse range of PcG complexes. Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes...
October 4, 2016: Cell Reports
https://www.readbyqxmd.com/read/27705745/rybp-stimulates-prc1-to-shape-chromatin-based-communication-between-polycomb-repressive-complexes
#18
Nathan R Rose, Hamish W King, Neil P Blackledge, Nadezda A Fursova, Katherine Ji Ember, Roman Fischer, Benedikt M Kessler, Robert J Klose
Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3)...
October 5, 2016: ELife
https://www.readbyqxmd.com/read/27659983/analysis-of-endogenous-protein-interactions-of-polycomb-group-of-proteins-in-mouse-embryonic-stem-cells
#19
Lluis Morey, Luciano Di Croce
PRC1 complexes contain four core subunits: Pcgf, Phc, Ring1, and Cbx proteins. Interestingly, mammalian genomes have several paralogues for each subunit, which are differentially expressed depending on the cell type, differentiation program, and cellular stimuli. Therefore, identification and characterization of the specific architecture of different PRC1 complexes during cellular differentiation are essential to better understand the function and recruitment mechanism of PRC1 complexes. In this chapter we describe several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27647897/bmi1-ubr5-axis-regulates-transcriptional-repression-at-damaged-chromatin
#20
Anthony Sanchez, Angelo De Vivo, Nadima Uprety, Jonghwan Kim, Stanley M Stevens, Younghoon Kee
BMI1 is a component of the Polycomb Repressive Complex 1 (PRC1), which plays a key role in maintaining epigenetic silencing during development. BMI1 also participates in gene silencing during DNA damage response, but the precise downstream function of BMI1 in gene silencing is unclear. Here we identified the UBR5 E3 ligase as a downstream factor of BMI1. We found that UBR5 forms damage-inducible nuclear foci in a manner dependent on the PRC1 components BMI1, RNF1 (RING1a), and RNF2 (RING1b). Whereas transcription is repressed at UV-induced lesions on chromatin, depletion of the PRC1 members or UBR5 alone derepressed transcription elongation at these sites, suggesting that UBR5 functions in a linear pathway with PRC1 in inducing gene silencing at lesions...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
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