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https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#1
REVIEW
Miguel Vidal, Katharzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated to 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 (PRC) 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-k119
#2
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 mono-ubiquitination of H2A at residue K119 (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 UbE2E1C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069948/genomic-targeting-of-epigenetic-probes-using-a-chemically-tailored-cas9-system
#3
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 9, 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
#4
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
#5
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
#6
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
#7
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...
January 3, 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
#8
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
#9
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
#10
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
#11
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...
December 27, 2016: EMBO Reports
https://www.readbyqxmd.com/read/28007606/compositional-and-functional-diversity-of-canonical-prc1-complexes-in-mammals
#12
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
#13
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
https://www.readbyqxmd.com/read/27941795/smarca4-atpase-mutations-disrupt-direct-eviction-of-prc1-from-chromatin
#14
Benjamin Z Stanton, Courtney Hodges, Joseph P Calarco, Simon M G Braun, Wai Lim Ku, Cigall Kadoch, Keji Zhao, Gerald R Crabtree
Trithorax-group proteins and their mammalian homologs, including those in BAF (mSWI/SNF) complexes, are known to oppose the activity of Polycomb repressive complexes (PRCs). This opposition underlies the tumor-suppressive role of BAF subunits and is expected to contribute to neurodevelopmental disorders. However, the mechanisms underlying opposition to Polycomb silencing are poorly understood. Here we report that recurrent disease-associated mutations in BAF subunits induce genome-wide increases in PRC deposition and activity...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27941648/anaphase-b
#15
REVIEW
Jonathan M Scholey, Gul Civelekoglu-Scholey, Ingrid Brust-Mascher
Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical "modules" that cooperate to mediate pole-pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux...
December 8, 2016: Biology
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#16
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27923621/transcriptomic-analysis-of-gene-expression-profiles-of-stomach-carcinoma-reveal-abnormal-expression-of-mitotic-components
#17
Hongfei Tong, Jisheng Wang, Hui Chen, Zhaohong Wang, Henwei Fan, Zhonglin Ni
AIMS: In order to explore the etiology of gastric cancer on global gene expression level, we developed advanced bioinformatic analysis to investigate the variations of global gene expression and the interactions among them. MAIN METHODS: We downloaded the dataset GSE63288 from Gene Expression Omnibus (GEO) database which included 22 human gastric cancer and 22 healthy control samples. We identified the differential expression genes, and explored the Gene ontology (GO) and pathways of the differentially expressed genes...
December 3, 2016: Life Sciences
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#18
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
#19
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
#20
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
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