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https://www.readbyqxmd.com/read/28782042/polycomb-repressive-complex-1-modifies-transcription-of-active-genes
#1
Michelle Pherson, Ziva Misulovin, Maria Gause, Kathie Mihindukulasuriya, Amanda Swain, Dale Dorsett
This study examines the role of Polycomb repressive complex 1 (PRC1) at active genes. The PRC1 and PRC2 complexes are crucial for epigenetic silencing during development of an organism. They are recruited to Polycomb response elements (PREs) and establish silenced domains over several kilobases. Recent studies show that PRC1 is also directly recruited to active genes by the cohesin complex. Cohesin participates broadly in control of gene transcription, but it is unknown whether cohesin-recruited PRC1 also plays a role in transcriptional control of active genes...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28765367/polycomb-mediated-chromatin-loops-revealed-by-a-subkilobase-resolution-chromatin-interaction-map
#2
Kyle P Eagen, Erez Lieberman Aiden, Roger D Kornberg
The locations of chromatin loops in Drosophila were determined by Hi-C (chemical cross-linking, restriction digestion, ligation, and high-throughput DNA sequencing). Whereas most loop boundaries or "anchors" are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28758948/polycomb-repressor-complex-2-in-genomic-instability-and-cancer
#3
REVIEW
Zoe Veneti, Kalliopi K Gkouskou, Aristides G Eliopoulos
Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene expression, and are widely recognized for their fundamental contributions to developmental processes. Herein, we summarize the existing evidence and molecular mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and malignancy, with a particular focus on the role of deregulated PRC2 in tumor suppressor gene expression, the DNA damage response, and the fidelity of DNA replication. We also discuss some of the recent advances in the development of pharmacological and dietary interventions affecting PRC2, which point to promising applications for the prevention and management of human malignancies...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28690110/mapping-load-bearing-in-the-mammalian-spindle-reveals-local-kinetochore-fiber-anchorage-that-provides-mechanical-isolation-and-redundancy
#4
Mary Williard Elting, Manu Prakash, Dylan B Udy, Sophie Dumont
Active forces generated at kinetochores move chromosomes, and the dynamic spindle must robustly anchor kinetochore fibers (k-fibers) to bear this load. The mammalian spindle bears the load of chromosome movement far from poles, but we do not know where and how-physically and molecularly-this load distributes across the spindle. In part, this is because probing spindle mechanics in live cells is difficult. Yet answering this question is key to understanding how the spindle generates and responds to force and performs its diverse mechanical functions...
July 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28670392/interactome-analysis-of-gene-expression-profiles-of-cervical-cancer-reveals-dysregulated-mitotic-gene-clusters
#5
Jing Cheng, Xiaosheng Lu, Jianguang Wang, Huina Zhang, Ping Duan, Chunyang Li
Cervical cancer is the second most common malignancy in women worldwide. HPV infections are the leading cause of cervical cancer. Although progress has been made in understanding cervical cancer, knowledge of oncogenic gene clusters that participate in squamous-cell mitosis is still lacking. We performed a computational analysis with qRT-PCR validation of gene expression profiles of cervical cancer tissues. Genes involved in muscle contraction and development were downregulated in cervical cancer tissues, suggesting decreased muscle function in cervical cancer...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28646916/prc1-contributes-to-tumorigenesis-of-lung-adenocarcinoma-in-association-with-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Ping Zhan, Bin Zhang, Guang-Min Xi, Ying Wu, Hong-Bing Liu, Ya-Fang Liu, Wu-Jian Xu, Qing-Qing Zhu, Feng Cai, Ze-Jun Zhou, Ying-Ying Miu, Xiao-Xia Wang, Jia-Jia Jin, Qian Li, Li-Ping Qian, Tang-Feng Lv, Yong Song
BACKGROUND: Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues...
June 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28602614/mir-203-interplays-with-polycomb-repressive-complexes-to-regulate-the-proliferation-of-neural-stem-progenitor-cells
#7
Pei-Pei Liu, Gang-Bin Tang, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Hong-Zhen Du, Zhao-Qian Teng, Chang-Mei Liu
The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28598616/identification-of-bmi1-promoter-inhibitors-from-beaumontia-murtonii-and-eugenia-operculata
#8
Yui Kaneta, Midori A Arai, Naoki Ishikawa, Kazufumi Toume, Takashi Koyano, Thaworn Kowithayakorn, Tetsuhiro Chiba, Atsushi Iwama, Masami Ishibashi
B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels...
June 9, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28596365/pcgf3-5-prc1-initiates-polycomb-recruitment-in-x-chromosome-inactivation
#9
Mafalda Almeida, Greta Pintacuda, Osamu Masui, Yoko Koseki, Michal Gdula, Andrea Cerase, David Brown, Arne Mould, Cassandravictoria Innocent, Manabu Nakayama, Lothar Schermelleh, Tatyana B Nesterova, Haruhiko Koseki, Neil Brockdorff
Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long noncoding RNAs. Here, we show that the noncanonical Polycomb group RING finger 3/5 (PCGF3/5)-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1-mediated ubiquitylation of histone H2A signals recruitment of other noncanonical PRC1 complexes and of PRC2, the latter leading to deposition of histone H3 lysine 27 methylation chromosome-wide...
June 9, 2017: Science
https://www.readbyqxmd.com/read/28588451/neurogenic-to-gliogenic-fate-transition-perturbed-by-loss-of-hmgb2
#10
Robert Bronstein, Jackson Kyle, Ariel B Abraham, Stella E Tsirka
Mouse cortical development relies heavily on a delicate balance between neurogenesis and gliogenesis. The lateral ventricular zone produces different classes of excitatory pyramidal cells until just before birth, when the production of astroglia begins to prevail. Epigenetic control of this fate shift is of critical importance and chromatin regulatory elements driving neuronal or astroglial development play an vital role. Different classes of chromatin binding proteins orchestrate the transcriptional repression of neuronal-specific genes, while allowing for the activation of astrocyte-specific genes...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28580277/expression-and-functional-assessment-of-candidate-type-2-diabetes-susceptibility-genes-identify-four-new-genes-contributing-to-human-insulin-secretion
#11
Fatou K Ndiaye, Ana Ortalli, Mickaël Canouil, Marlène Huyvaert, Clara Salazar-Cardozo, Cécile Lecoeur, Marie Verbanck, Valérie Pawlowski, Raphaël Boutry, Emmanuelle Durand, Iandry Rabearivelo, Olivier Sand, Lorella Marselli, Julie Kerr-Conte, Vikash Chandra, Raphaël Scharfmann, Odile Poulain-Godefroy, Piero Marchetti, François Pattou, Amar Abderrahmani, Philippe Froguel, Amélie Bonnefond
OBJECTIVES: Genome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28577303/hhex-regulates-hematopoietic-stem-cell-self-renewal-and-stress-hematopoiesis-via-repression-of-cdkn2a
#12
Jacob T Jackson, Benjamin J Shields, Wei Shi, Ladina Di Rago, Donald Metcalf, Nicos A Nicola, Matthew P McCormack
The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal...
August 2017: Stem Cells
https://www.readbyqxmd.com/read/28513584/kinesin-5-independent-mitotic-spindle-assembly-requires-the-antiparallel-microtubule-crosslinker-ase1-in-fission-yeast
#13
Sergio A Rincon, Adam Lamson, Robert Blackwell, Viktoriya Syrovatkina, Vincent Fraisier, Anne Paoletti, Meredith D Betterton, Phong T Tran
Bipolar spindle assembly requires a balance of forces where kinesin-5 produces outward pushing forces to antagonize the inward pulling forces from kinesin-14 or dynein. Accordingly, Kinesin-5 inactivation results in force imbalance leading to monopolar spindle and chromosome segregation failure. In fission yeast, force balance is restored when both kinesin-5 Cut7 and kinesin-14 Pkl1 are deleted, restoring spindle bipolarity. Here we show that the cut7Δpkl1Δ spindle is fully competent for chromosome segregation independently of motor activity, except for kinesin-6 Klp9, which is required for anaphase spindle elongation...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28505103/neuronal-migration-and-auts2-syndrome
#14
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/28491069/characterization-of-the-polycomb-group-mark-h3k27me3-in-unicellular-algae
#15
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/28483375/mechanisms-regulating-prc2-recruitment-and-enzymatic-activity
#16
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/28440749/correction-pcgf6-prc1-suppresses-premature-differentiation-of-mouse-embryonic-stem-cells-by-regulating-germ-cell-related-genes
#17
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
No abstract text is available yet for this article.
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#18
REVIEW
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28422978/the-escrt-regulator-did2-maintains-the-balance-between-long-distance-endosomal-transport-and-endocytic-trafficking
#19
Carl Haag, Thomas Pohlmann, Michael Feldbrügge
In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28412742/association-of-the-long-non-coding-rna-malat1-with-the-polycomb-repressive-complex-pathway-in-t-and-nk-cell-lymphoma
#20
Soo Hee Kim, Se Hoon Kim, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
Recently, various long non-coding RNAs (lncRNAs) have been reported to have significant therapeutic or prognostic value. However, the expression of lncRNAs has not been investigated in T and NK cell lymphoma. Thus, we evaluated the biological and prognostic role of lncRNAs related to the polycomb repressive complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical samples and cell lines. High expression of MALAT1 as well as BMI1 was related to poor prognosis in patients with mature T cell lymphoma...
May 9, 2017: Oncotarget
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