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https://www.readbyqxmd.com/read/28396698/internal-modifications-in-the-cenp-a-nucleosome-modulate-centromeric-dynamics
#1
Minh Bui, Mary Pitman, Arthur Nuccio, Serene Roque, Paul Gregory Donlin-Asp, Aleksandra Nita-Lazar, Garegin A Papoian, Yamini Dalal
BACKGROUND: Posttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 variant CENP-A, few modifications have been reported, and their functions remain largely unexplored. In this multidisciplinary report, we utilize in silico computational and in vivo approaches to dissect lysine 124 of human CENP-A, which was previously reported to be acetylated in advance of replication...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28395724/-single-nucleotide-polymorphism-of-stat4-rs7574865-is-associated-with-the-susceptibility-of-primary-biliary-cirrhosis-in-han-population-of-partial-regions-of-jiangsu-province
#2
Liming Zheng, Hong Zhou
Objective To investigate the correlation of single nucleotide polymorphism (SNP) of signal transducer and activator of transcription 4 (STAT4) rs7574865 gene with primary biliary cirrhosis (PBC) in Han population of Jiangsu province. Methods The peripheral blood samples were collected from 138 inpatients with PBC and 116 unrelated healthy donors in the Third People's Hospital of Changzhou City in Jiangsu province. The STAT4 rs7574865 SNP was determined by polymerase chain reaction-sequence specific primer (PCR-SSP) assay...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#3
Frances Spiller, Bethan Medina-Pritchard, Maria Alba Abad, Martin A Wear, Oscar Molina, William C Earnshaw, A Arockia Jeyaprakash
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex...
April 4, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28356341/essential-role-for-centromeric-factors-following-p53-loss-and-oncogenic-transformation
#4
Dan Filipescu, Monica Naughtin, Katrina Podsypanina, Vincent Lejour, Laurence Wilson, Zachary A Gurard-Levin, Guillermo A Orsi, Iva Simeonova, Eleonore Toufektchan, Laura D Attardi, Franck Toledo, Geneviève Almouzni
In mammals, centromere definition involves the histone variant CENP-A (centromere protein A), deposited by its chaperone, HJURP (Holliday junction recognition protein). Alterations in this process impair chromosome segregation and genome stability, which are also compromised by p53 inactivation in cancer. Here we found that CENP-A and HJURP are transcriptionally up-regulated in p53-null human tumors. Using an established mouse embryonic fibroblast (MEF) model combining p53 inactivation with E1A or HRas-V12 oncogene expression, we reproduced a similar up-regulation of HJURP and CENP-A...
March 29, 2017: Genes & Development
https://www.readbyqxmd.com/read/28321116/chromosome-biology-trimethylation-of-cenp-a-supports-mitotic-fidelity
#5
Paulina Strzyz
No abstract text is available yet for this article.
March 21, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28296274/relevance-of-clinical-and-autoantibody-profiles-in-systemic-sclerosis-among-thais
#6
Chingching Foocharoen, Piyakarn Watcharenwong, Sittichai Netwijitpan, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Ratanavadee Nanagara
OBJECTIVE: Autoantibody profiles in systemic sclerosis (SSc) and their relative clinical association vary between studies. The rate for being anti-topoisomerase-I (ATA) positive and the association with diffuse cutaneous the SSc subset (dcSSc) is higher among Thais than among Caucasians. The objective was to evaluate the relevance of clinical presentation, namely being positive for one or more autoantibodies among Thai SSc patients. METHOD: A retrospective, cohort study was performed among SSc patients over 18 years of age at Srinagarind Hospital, Khon Kaen University, Thailand, during January 2006 to December 2013...
March 10, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#7
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28266506/%C3%AE-amino-trimethylation-of-cenp-a-by-nrmt-is-required-for-full-recruitment-of-the-centromere
#8
Kizhakke M Sathyan, Daniele Fachinetti, Daniel R Foltz
Centromeres are unique chromosomal domains that control chromosome segregation, and are epigenetically specified by the presence of the CENP-A containing nucleosomes. CENP-A governs centromere function by recruiting the constitutive centromere associated network (CCAN) complex. The features of the CENP-A nucleosome necessary to distinguish centromeric chromatin from general chromatin are not completely understood. Here we show that CENP-A undergoes α-amino trimethylation by the enzyme NRMT in vivo. We show that α-amino trimethylation of the CENP-A tail contributes to cell survival...
March 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28265097/stepwise-unfolding-supports-a-subunit-model-for-vertebrate-kinetochores
#9
Giulia Vargiu, Alexandr A Makarov, James Allan, Tatsuo Fukagawa, Daniel G Booth, William C Earnshaw
During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constriction of chromosomes. In addition to the centromere histone centromere protein A (CENP-A), 15 other members of the constitutive centromere associated network (CCAN) participate in the formation of a chromatin-associated scaffold that supports kinetochore structure. We performed a targeted screen analyzing unfolded centrochromatin from CENP-depleted chromosomes...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28259924/mutational-spectrum-of-cenp-b-box-and-%C3%AE-satellite-dna-on-chromosome-21-in-down-syndrome-children
#10
Qian Chen, Bin Tan, Jun-Lin He, Xue-Qing Liu, Xue-Mei Chen, Ru-Fei Gao, Jing Zhu, Ying-Xiong Wang, Hong-Bo Qi
The centromere is responsible for the correct inheritance of eukaryotic chromosomes during cell division. Centromere protein B (CENP‑B) and its 17 base pair binding site (CENP‑B box), which appears at regular intervals in centromeric α-satellite DNA (α-satDNA), are important for the assembly of the centromere components. Therefore, it is conceivable that CENP-B box mutations may induce errors in cell division. However, the association between the deoxynucleotide alterations of the CENP‑B box and the extra chromosome 21 (Chr21) present in patients with Down syndrome (DS) remains to be elucidated...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28235947/human-centromeric-cenp-a-chromatin-is-a-homotypic-octameric-nucleosome-at-all-cell-cycle-points
#11
Yael Nechemia-Arbely, Daniele Fachinetti, Karen H Miga, Nikolina Sekulic, Gautam V Soni, Dong Hyun Kim, Adeline K Wong, Ah Young Lee, Kristen Nguyen, Cees Dekker, Bing Ren, Ben E Black, Don W Cleveland
Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28220502/variations-on-a-nucleosome-theme-the-structural-basis-of-centromere-function
#12
Olga Moreno-Moreno, Mònica Torras-Llort, Fernando Azorín
The centromere is a specialized chromosomal structure that dictates kinetochore assembly and, thus, is essential for accurate chromosome segregation. Centromere identity is determined epigenetically by the presence of a centromere-specific histone H3 variant, CENP-A, that replaces canonical H3 in centromeric chromatin. Here, we discuss recent work by Roulland et al. that identifies structural elements of the nucleosome as essential determinants of centromere function. In particular, CENP-A nucleosomes have flexible DNA ends due to the short αN helix of CENP-A...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28218637/mechanisms-of-chromosome-congression-during-mitosis
#13
REVIEW
Helder Maiato, Ana Margarida Gomes, Filipe Sousa, Marin Barisic
Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression...
February 17, 2017: Biology
https://www.readbyqxmd.com/read/28217959/anti-rnpc3-antibodies-as-a-marker-of-cancer-associated-scleroderma
#14
Ami A Shah, George Xu, Antony Rosen, Laura K Hummers, Fredrick M Wigley, Stephen J Elledge, Livia Casciola-Rosen
INTRODUCTION: Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with RNA polymerase III (POL) autoantibodies and in patients negative for anti-centromere (CENP), anti-topoisomerase-1 (TOPO), and anti-POL antibodies (referred to as CENP/TOPO/POL (CTP)-Negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, we found that 25% had autoantibodies to RNPC3, a member of the minor spliceosome complex. In this investigation, we validated the relationship between anti-RNPC3 antibodies and cancer and examined the associated clinical phenotype in a large sample of scleroderma patients...
February 19, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28186195/cenp-a-chromatin-disassembly-in-stressed-and-senescent-murine-cells
#15
Sabrine Hédouin, Giacomo Grillo, Ivana Ivkovic, Guillaume Velasco, Claire Francastel
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong and selective transcriptional activation of centromeric repeats is detected within hours. This is followed by disorganization of centromeres with striking delocalization of nucleosomal CENP-A, the key determinant of centromere identity and function, in a mechanism requiring active transcription of centromeric repeats, the DNA Damage Response (DDR) effector ATM and chromatin remodelers/histone chaperones...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167779/integrity-of-the-human-centromere-dna-repeats-is-protected-by-cenp-a-cenp-c-and-cenp-t
#16
Simona Giunta, Hironori Funabiki
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28158539/defects-in-methylation-of-arginine-37-on-cenp-a-cse4-are-compensated-by-the-ubiquitin-ligase-complex-ubr2-mub1
#17
Anke Samel, Thi Kim Loan Nguyen, Ann E Ehrenhofer-Murray
No abstract text is available yet for this article.
February 2, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28137567/mass-spectrometry-based-methodology-for-identification-of-native-histone-variant-modifications-from-mammalian-tissues-and-solid-tumors
#18
A G Nuccio, M Bui, Y Dalal, A Nita-Lazar
Histone posttranslational modifications (PTMs) are key epigenetic marks involved in gene silencing or activation. Histone modifications impact chromatin organization and transcriptional processes through the changes in charge density between histones and DNA. They also serve as recognition and binding sites for specific binding proteins. Histone tails and globular cores contain many basic amino acid residues, which are subject to various dynamic modifications, making the modification repertoire extremely diverse...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28125646/kif4-is-essential-for-mouse-oocyte-meiosis
#19
Nicole J Camlin, Eileen A McLaughlin, Janet E Holt
Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development...
2017: PloS One
https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#20
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
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