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https://www.readbyqxmd.com/read/28098861/triptolide-inhibits-viability-and-induces-apoptosis-in-liver-cancer-cells-through-activation-of-the-tumor-suppressor-gene-p53
#1
Yan-Yan Sun, Lei Xiao, Dong Wang, Yan-Chao Ji, Yu-Peng Yang, Rong Ma, Xi-Hai Chen
The present study investigated the effect of triptolide on viability and apoptosis along with underlying mechanism in liver cancer cells. CCK-8 assay showed that triptolide treatment for 48 h significantly reduced the viability of HepG2 and QSG7701 cells at 50 µM concentration. Annexin V-FITC and propidium iodide staining showed that triptolide treatment of HepG2 cells at 50 µM concentrations induced apoptosis in 56.45% cells compared to only 2.36% cells in the control cultures. Western blot assay showed that treatment of HepG2 cells with 50 µM concentration of triptolide significantly induced phosphorylation of p53 in a 2 h-treatment...
January 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098859/dna-damage-response-defect-in-williams-beuren-syndrome
#2
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
January 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#3
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/28079247/dynamic-location-changes-of-bub1-phosphorylated-h2athr133-with-cenh3-nucleosome-in-maize-centromeric-regions
#4
Handong Su, Yalin Liu, Qianhua Dong, Chao Feng, Jing Zhang, Yang Liu, James A Birchler, Fangpu Han
The genomic stability of all organisms requires precise cell division with proper chromosome orientation. The Bub1-H2Aph-Sgo1 pathway and spindle assembly checkpoint (SAC) components have been identified in yeast and mammals that are important for sister centromere orientation and chromosome segregation. However, their roles in plants are not clear. Maize meiotic mutants and minichromosomes were used to study the role of H2AThr133 phosphorylation and SAC components in sister centromere orientation and chromosome segregation...
January 12, 2017: New Phytologist
https://www.readbyqxmd.com/read/28074910/myosin-phosphatase-and-rhoa-activated-kinase-modulate-arginine-methylation-by-the-regulation-of-protein-arginine-methyltransferase-5-in-hepatocellular-carcinoma-cells
#5
Adrienn Sipos, Judit Iván, Bálint Bécsi, Zsuzsanna Darula, István Tamás, Dániel Horváth, Katalin F Medzihradszky, Ferenc Erdődi, Beáta Lontay
Myosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-k119
#6
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/28067802/stabilization-of-nucleosomes-by-histone-tails-and-by-fact-revealed-by-spfret-microscopy
#7
Maria E Valieva, Nadezhda S Gerasimova, Kseniya S Kudryashova, Anastasia L Kozlova, Mikhail P Kirpichnikov, Qi Hu, Maria Victoria Botuyan, Georges Mer, Alexey V Feofanov, Vasily M Studitsky
A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers...
January 6, 2017: Cancers
https://www.readbyqxmd.com/read/28066899/a-role-for-the-histone-h2a-deubiquitinase-mysm1-in-maintenance-of-cd8-t-cells
#8
Michael Förster, Rupinder K Boora, Jessica C Petrov, Nassima Fodil, Isabella Albanese, Jamie Kim, Philippe Gros, Anastasia Nijnik
Several previous studies outlined the importance of the histone H2A deubiquitinase (H2A-DUB) MYSM1 in the regulation of stem cell quiescence and hematopoiesis. In this study we investigated the role of MYSM1 in T cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM1 is intricately involved in the maintenance, activation, and survival of CD8+ T cells. Mysm1 ablation resulted in a 2-fold reduction in CD8+ T cell numbers, and also led to a hyperactivated CD8+ T cell state accompanied by impaired proliferation and increased proinflammatory cytokine production after ex vivo stimulation...
January 9, 2017: Immunology
https://www.readbyqxmd.com/read/28063982/proteomic-analysis-of-lysine-succinylation-of-the-human-pathogen-histoplasma-capsulatum
#9
Longxiang Xie, Juan Li, Wanyan Deng, Zhaoxiao Yu, Wenjie Fang, Min Chen, Wanqing Liao, Jianping Xie, Weihua Pan
: Histoplasma capsulatum, the causative agent of histoplasmosis (also called "Darling's disease"), can affect both immunocompetent and immunocompromised hosts. Post-translational protein modification by lysine succinylation (Ksuc) is a frequent occurrence in eukaryote and prokaryote. Recently, the roles of succinylation and its regulatory enzymes in regulating metabolic pathway in bacteria, mammalian and fungus were highlighted. Here, we report the first global profiling of lysine succinylation, with 463 modification sites in 202 proteins from H...
January 4, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28040741/premature-silencing-of-the-spindle-assembly-checkpoint-is-prevented-by-the-bub1-h2a-sgo1-pp2a-axis-in-saccharomyces-cerevisiae
#10
Fengzhi Jin, Michael Bokros, Yanchang Wang
The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment that applies tension on kinetochores. Our previous data in budding yeast Saccharomyces cerevisiae show that Ipl1/Aurora B kinase and a centromere-associated protein Sgo1 are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete...
December 30, 2016: Genetics
https://www.readbyqxmd.com/read/28038734/partially-assembled-nucleosome-structures-at%C3%A2-atomic-detail
#11
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
December 27, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/28033404/plasmodium-falciparum-nucleosomes-exhibit-reduced-stability-and-lost-sequence-dependent-nucleosome-positioning
#12
Elisabeth Silberhorn, Uwe Schwartz, Patrick Löffler, Samuel Schmitz, Anne Symelka, Tania de Koning-Ward, Rainer Merkl, Gernot Längst
The packaging and organization of genomic DNA into chromatin represents an additional regulatory layer of gene expression, with specific nucleosome positions that restrict the accessibility of regulatory DNA elements. The mechanisms that position nucleosomes in vivo are thought to depend on the biophysical properties of the histones, sequence patterns, like phased di-nucleotide repeats and the architecture of the histone octamer that folds DNA in 1.65 tight turns. Comparative studies of human and P. falciparum histones reveal that the latter have a strongly reduced ability to recognize internal sequence dependent nucleosome positioning signals...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/28032848/the-chd1-chromatin-remodeler-shifts-hexasomes-unidirectionally
#13
Robert F Levendosky, Anton Sabantsev, Sebastian Deindl, Gregory D Bowman
Despite their canonical two-fold symmetry, nucleosomes in biological contexts are often asymmetric: functionalized with post-translational modifications (PTMs), substituted with histone variants, and even lacking H2A/H2B dimers. Here we show that the Widom 601 nucleosome positioning sequence can produce hexasomes in a specific orientation on DNA, providing a useful tool for interrogating chromatin enzymes and allowing for the generation of nucleosomes with precisely defined asymmetry. Using this methodology, we demonstrate that the Chd1 chromatin remodeler from Saccharomyces cerevisiae requires H2A/H2B on the entry side for sliding, and thus, unlike the back-and-forth sliding observed for nucleosomes, Chd1 shifts hexasomes unidirectionally...
December 29, 2016: ELife
https://www.readbyqxmd.com/read/28032293/spatiotemporal-patterns-of-ring1-expression-after-rat-spinal-cord-injury
#14
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
#15
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/28028239/asymmetric-unwrapping-of-nucleosomal-dna-propagates-asymmetric-opening-and-dissociation-of-the-histone-core
#16
Yujie Chen, Joshua M Tokuda, Traci Topping, Steve P Meisburger, Suzette A Pabit, Lisa M Gloss, Lois Pollack
The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28025392/ino80-represses-osmostress-induced-gene-expression-by-resetting-promoter-proximal-nucleosomes
#17
Eva Klopf, Heiko A Schmidt, Sandra Clauder-Münster, Lars M Steinmetz, Christoph Schüller
The conserved INO80 chromatin remodeling complex is involved in regulation of DNA damage repair, replication and transcription. It is commonly recruited to the transcription start region and contributes to the establishment of promoter-proximal nucleosomes. We find a substantial influence of INO80 on nucleosome dynamics and gene expression during stress induced transcription. Transcription induced by osmotic stress leads to genome-wide remodeling of promoter proximal nucleosomes. INO80 function is required for timely return of evicted nucleosomes to the 5' end of induced genes...
December 25, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/28009280/three-dimensional-architecture-of-the-human-brca1-a-histone-deubiquitinase-core-complex
#18
Otto J P Kyrieleis, Pauline B McIntosh, Sarah R Webb, Lesley J Calder, Janette Lloyd, Nisha A Patel, Stephen R Martin, Carol V Robinson, Peter B Rosenthal, Stephen J Smerdon
BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached to histone H2A and H2AX. BRCA1-A contributes to checkpoint regulation, repair pathway choice, and HR repair efficiency through molecular mechanisms that remain largely obscure. The structure of an active core complex comprising two Abraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas/BRCC36 heterodimers sits at the base, with BRCC45/Merit40 pairs occupying each arm...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28001079/profiling-of-histone-post-translational-modifications-in-mouse-brain-with-high-resolution-top-down-mass-spectrometry
#19
Mowei Zhou, Ljiljana Paša-Tolić, David L Stenoien
As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms...
December 21, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27997336/transcriptional-signatures-of-somatic-neoblasts-and-germline-cells-in-macrostomum-lignano
#20
Magda Grudniewska, Stijn Mouton, Daniil Simanov, Frank Beltman, Margriet Grelling, Katrien de Mulder, Wibowo Arindrarto, Philipp M Weissert, Stefan van der Elst, Eugene Berezikov
The regeneration-capable flatworm Macrostomum lignano is a powerful model organism to study the biology of stem cells in vivo. As a flatworm amenable to transgenesis, it complements the historically used planarian flatworm models, such as Schmidtea mediterranea. However, information on the transcriptome and markers of stem cells in M. lignano is limited. We generated a de novo transcriptome assembly and performed the first comprehensive characterization of gene expression in the proliferating cells of M. lignano, represented by somatic stem cells, called neoblasts, and germline cells...
December 20, 2016: ELife
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