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https://www.readbyqxmd.com/read/28329686/demethylated-hsatii-dna-and-hsatii-rna-foci-sequester-prc1-and-mecp2-into-cancer-specific-nuclear-bodies
#1
Lisa L Hall, Meg Byron, Dawn M Carone, Troy W Whitfield, Gayle P Pouliot, Andrew Fischer, Peter Jones, Jeanne B Lawrence
This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28304275/pcgf6-prc1-suppresses-premature-differentiation-of-mouse-embryonic-stem-cells-by-regulating-germ-cell-related-genes
#2
Mitsuhiro Endoh, Takaho A Endo, Jun Shinga, Katsuhiko Hayashi, Anca Farcas, Kit-Wan Ma, Shinsuke Ito, Jafar Sharif, Tamie Endoh, Naoko Onaga, Manabu Nakayama, Tomoyuki Ishikura, Osamu Masui, Benedikt M Kessler, Toshio Suda, Osamu Ohara, Akihiko Okuda, Robert J Klose, Haruhiko Koseki
The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability...
March 17, 2017: ELife
https://www.readbyqxmd.com/read/28262675/genomic-characterisation-of-e%C3%AE-myc-mouse-lymphomas-identifies-bcor-as-a-myc-co-operative-tumour-suppressor-gene
#3
Marcus Lefebure, Richard W Tothill, Elizabeth Kruse, Edwin D Hawkins, Jake Shortt, Geoffrey M Matthews, Gareth P Gregory, Benjamin P Martin, Madison J Kelly, Izabela Todorovski, Maria A Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev Kats, Micah D Gearhart, Vivian J Bardwell, Ross A Dickins, Ross D Hannan, Anthony T Papenfuss, Ricky W Johnstone
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28202673/molecular-architecture-of-polycomb-repressive-complexes
#4
REVIEW
Emily C Chittock, Sebastian Latwiel, Thomas C R Miller, Christoph W Müller
The polycomb group (PcG) proteins are a large and diverse family that epigenetically repress the transcription of key developmental genes. They form three broad groups of polycomb repressive complexes (PRCs) known as PRC1, PRC2 and Polycomb Repressive DeUBiquitinase, each of which modifies and/or remodels chromatin by distinct mechanisms that are tuned by having variable compositions of core and accessory subunits. Until recently, relatively little was known about how the various PcG proteins assemble to form the PRCs; however, studies by several groups have now allowed us to start piecing together the PcG puzzle...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28157505/polycomb-repressive-complex-1-generates-discrete-compacted-domains-that-change-during-differentiation
#5
Sharmistha Kundu, Fei Ji, Hongjae Sunwoo, Gaurav Jain, Jeannie T Lee, Ruslan I Sadreyev, Job Dekker, Robert E Kingston
Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1)...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28157500/a-finer-print-than-tads-prc1-mediated-domains
#6
Elena Torlai Triglia, Tiago Rito, Ana Pombo
Polycomb proteins are well-known epigenetic repressors with unexplained roles in chromatin folding. In this issue of Molecular Cell, Kundu et al. (2017) investigate the structures of PRC1-mediated domains in stem cells and probe their changes upon differentiation and in PRC knockouts.
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28111200/rna-helicase-ddx5-inhibits-reprogramming-to-pluripotency-by-mirna-based-repression-of-rybp-and-its-prc1-dependent-and-independent-functions
#7
Huanhuan Li, Ping Lai, Jinping Jia, Yawei Song, Qing Xia, Kaimeng Huang, Na He, Wangfang Ping, Jiayu Chen, Zhongzhou Yang, Jiao Li, Mingze Yao, Xiaotao Dong, Jicheng Zhao, Chunhui Hou, Miguel A Esteban, Shaorong Gao, Duanqing Pei, Andrew P Hutchins, Hongjie Yao
RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119...
January 11, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#8
REVIEW
Miguel Vidal, Katarzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated with reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRCs) endowed with distinct histone-tail-modifying activities...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-lys-119
#9
Keith Wheaton, Feroz Sarkari, Beena Stanly Johns, Hossein Davarinejad, Olga Egorova, Lilia Kaustov, Brian Raught, Vivian Saridakis, Yi Sheng
UbE2E1/UbcH6 is an E2 ubiquitin-conjugating enzyme that is regulated by USP7. We identified UbE2E1 as a novel component of Polycomb repressive complex 1 (PRC1), the E3 ligase complex responsible for histone H2A ubiquitination and gene silencing. We demonstrate that UbE2E1 is critical for the monoubiquitination of H2A at residue Lys-119 (uH2AK119) through its association with the PRC1 complex. UbE2E1 interacts with PRC1 subunits including Ring1A and Ring1B. Overexpression of UbE2E1 results in increased levels of uH2AK119, whereas overexpression of catalytically inactive UbE2E1_C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069948/genomic-targeting-of-epigenetic-probes-using-a-chemically-tailored-cas9-system
#10
Glen P Liszczak, Zachary Z Brown, Samuel H Kim, Rob C Oslund, Yael David, Tom W Muir
Recent advances in the field of programmable DNA-binding proteins have led to the development of facile methods for genomic localization of genetically encodable entities. Despite the extensive utility of these tools, locus-specific delivery of synthetic molecules remains limited by a lack of adequate technologies. Here we combine the flexibility of chemical synthesis with the specificity of a programmable DNA-binding protein by using protein trans-splicing to ligate synthetic elements to a nuclease-deficient Cas9 (dCas9) in vitro and subsequently deliver the dCas9 cargo to live cells...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069891/governing-the-silencing-state-of-chromatin-the-roles-of-polycomb-repressive-complex-1-in-arabidopsis
#11
Xianli Yang, Aizi Tong, Bowen Yan, Xiaoxue Wang
Polycomb group proteins form multiple protein complexes such as polycomb repressive complex (PRC) 1 and PRC2, which repress the expression of thousands of genes. PRC1 and PRC2 are essential for normal development in Arabidopsis Recently, significant progress has been made in understanding the functions and regulatory mechanisms of PRC1. In this review, we focus on the discovery of the composition of PRC1, functions of its components, the recruitment of PRC1 to target genes, and the control of PRC1 function in Arabidopsis Perspectives on dissecting the roles of PRC1 in plant gene expression and development are also given...
January 9, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28061449/central-spindle-proteins-and-mitotic-kinesins-are-direct-transcriptional-targets-of-muvb-b-myb-and-foxm1-in-breast-cancer-cell-lines-and-are-potential-targets-for-therapy
#12
Patrick Wolter, Steffen Hanselmann, Grit Pattschull, Eva Schruf, Stefan Gaubatz
The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059125/neuronal-apoptosis-inhibitory-protein-naip-localizes-to-the-cytokinetic-machinery-during-cell-division
#13
Francisco Abadía-Molina, Virginia Morón-Calvente, Stephen D Baird, Fahad Shamim, Francisco Martín, Alex MacKenzie
The neuronal apoptosis inhibitory protein (NAIP) is a constituent of the inflammasome and a key component of the innate immune system. Here we use immunofluorescence to position NAIP within the cytokinetic apparatus, contiguous to chromosomal passenger complex (CPC), Centralspindlin, PRC1 and KIF4A. During metaphase, NAIP accumulates in the mitotic spindle poles and is shown in spindle microtubules; in anaphase NAIP is detected in the middle of the central spindle. At the end of cytokinesis, NAIP is localized in the outlying region of the stem body, the center of the intercellular bridge formed between daughter cells prior to cellular abscission...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049731/essential-role-for-polycomb-group-protein-pcgf6-in-embryonic-stem-cell-maintenance-and-a-noncanonical-polycomb-repressive-complex-1-prc1-integrity
#14
Wukui Zhao, Huan Tong, Yikai Huang, Yun Yan, Huajian Teng, Yin Xia, Qing Jiang, Jinzhong Qin
The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation, and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs, and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28040729/polycomb-repressive-complex-1-provides-a-molecular-explanation-for-repeat-copy-number-dependency-in-fshd-muscular-dystrophy
#15
Valentina Casa, Valeria Runfola, Stefano Micheloni, Arif Aziz, F Jeffrey Dilworth, Davide Gabellini
Repression of repetitive elements is crucial to preserve genome integrity and has been traditionally ascribed to constitutive heterochromatin pathways. FacioScapuloHumeral Muscular Dystrophy (FSHD), one of the most common myopathies, is characterized by a complex interplay of genetic and epigenetic events. The main FSHD form is linked to reduced copy number of the D4Z4 macrosatellite repeat on 4q35, causing loss of silencing and aberrant expression of the D4Z4-embedded DUX4 gene leading to disease. By an unknown mechanism, D4Z4 copy-number correlates with FSHD phenotype...
December 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28032293/spatiotemporal-patterns-of-ring1-expression-after-rat-spinal-cord-injury
#16
Hanzhang Liu, Wei Ji, Peipei Gong, Chun Liu, Chengwei Duan, Yilu Gao, Xiaojuan Liu, Dongmei Zhang, Shunxing Zhu, Leilei Gong
Ring finger protein 1 (RING1) is a RING domain characterized protein belonging to the RING finger family. It is an E3 ubiquitin-protein ligase that mediated monoubiquitination of histone H2A and the core component of PRC1 complex, which is the repressive multiprotein complex of Polycomb group (PcG). Previous studies showed the important tumorigenic role of RING1 via promoting cell proliferation and the crucial function in maintaining transcriptional program stability during development. However, its mechanism for spinal cord injury (SCI) is still unknown...
December 28, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28029659/knockdown-of-rnf2-induces-cell-cycle-arrest-and-apoptosis-in-prostate-cancer-cells-through-the-upregulation-of-txnip
#17
Ming Wei, Dian Jiao, Donghui Han, Jieheng Wu, Feilong Wei, Guoxu Zheng, Zhangyan Guo, Wenjin Xi, Fa Yang, Pin Xie, Lingling Zhang, An-Gang Yang, He Wang, Weijun Qin, Weihong Wen
RNF2, also known as RING1b or RING2, is identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), which mediates the mono-ubiquitination of histone H2A. RNF2 has been proved to have oncogenic function in many kinds of cancers, but the function of RNF2 in prostate cancer (PCa) has not been evaluated. Here we show that PCa tissues showed higher RNF2 expression than the benign prostatic hyperplasia (BPH) tissues. Knockdown of RNF2 in PCa cells resulted in cell cycle arrest, increased apoptosis and inhibited cell proliferation, and the growth of RNF2 knockdown PCa xenografts were obviously inhibited in nude mice...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028032/prc1-labeled-microtubule-bundles-and-kinetochore-pairs-show-one-to-one-association-in-metaphase
#18
Bruno Polak, Patrik Risteski, Sonja Lesjak, Iva M Tolić
In the mitotic spindle, kinetochore microtubules form k-fibers, whereas overlap or interpolar microtubules form antiparallel arrays containing the cross-linker protein regulator of cytokinesis 1 (PRC1). We have recently shown that an overlap bundle, termed bridging fiber, links outermost sister k-fibers. However, the relationship between overlap bundles and k-fibers throughout the spindle remained unknown. Here, we show that in a metaphase spindle more than 90% of overlap bundles act as a bridge between sister k-fibers...
February 2017: EMBO Reports
https://www.readbyqxmd.com/read/28007606/compositional-and-functional-diversity-of-canonical-prc1-complexes-in-mammals
#19
REVIEW
Katelyn E Connelly, Emily C Dykhuizen
The compositional complexity of Polycomb Repressive Complex 1 (PRC1) increased dramatically during vertebrate evolution. What is considered the "canonical" PRC1 complex consists of four subunits originally identified as regulators of body segmentation in Drosophila. In mammals, each of these four canonical subunits consists of two to six paralogs that associate in a combinatorial manner to produce over a hundred possible distinct PRC1 complexes with unknown function. Genetic studies have begun to define the phenotypic roles for different PRC1 paralogs; however, relating these phenotypes to unique biochemical and transcriptional function for the different paralogs has been challenging...
December 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28007029/arabidopsis-prc1-core-component-atring1-regulates-stem-cell-determining-carpel-development-mainly-through-repression-of-class-i-knox-genes
#20
Donghong Chen, Anne M Molitor, Lin Xu, Wen-Hui Shen
BACKGROUND: Polycomb repressive complex 2 (PRC2)-catalyzed H3K27me3 marks are tightly associated with the WUS-AG negative feedback loop to terminate floral stem cell fate to promote carpel development, but the roles of Polycomb repressive complex 1 (PRC1) in this event remain largely uncharacterized. RESULTS: Here we show conspicuous variability in the morphology and number of carpels among individual flowers in the absence of the PRC1 core components AtRING1a and AtRING1b, which contrasts with the wild-type floral meristem consumed by uniform carpel production in Arabidopsis thaliana...
December 22, 2016: BMC Biology
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