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https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#1
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28185200/automated-high-content-screening-of-%C3%AE-h2ax-expression-in-hela-cells
#2
Nate Hopp, Jodi Hagen, Birte Aggeler, Alexander E Kalyuzhny
Due to their inherent nature, DNA strands can be easily broken by various environmental factors including chemical agents and ionizing radiation. Unrepaired DNA double-stranded breaks (DSBs) may result in genetic instability and have a strong negative impact on the integrity of the genome. It has been found that DSBs are always followed by phosphorylation of histone protein H2AX, a member of the H2A family, and immunocytochemical detection of phosphorylated H2AX (referred to as γ-H2AX) is one of the frequently used techniques for assessing DNA damage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28178526/crl4-dcaf8-ubiquitin-ligase-targets-histone-h3k79-and-promotes-h3k9-methylation-in-the-liver
#3
Gaofeng Li, Tong Ji, Jiang Chen, Yufei Fu, Lidan Hou, Yan Feng, Tingyue Zhang, Tianyu Song, Jie Zhao, Yoko Endo, Hui Lin, Xiujun Cai, Yong Cang
Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177835/analysis-of-the-histone-cluster-in-senegalese-sole-solea-senegalensis-evidence-for-a-divergent-evolution-of-two-canonical-histone-clusters
#4
Manuel Alejandro Merlo, Roger Iziga, Silvia Portela, Ismael Cross, Nadezda Kosyakova, Thomas Liehr, Manuel Manchado, Laureana Rebordinos
The Senegalese sole (Solea senegalensis) is commercially very important, and is a priority species for aquaculture product diversification. The main histone cluster was found in two BAC clones. However, two replacement histones (H1.0 and H3.3) were found in another BAC clone. Different types of canonical H2A and H2B have been found in one species for the first time. Phylogenetic analysis demonstrated that the different H1, H2A and H2B types were all more similar to each other than to canonical histones from other species...
December 10, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28177753/histone-h3-3-regulates-mitotic-progression-in-mouse-embryonic-fibroblasts
#5
Aysegul Ors, Christophe Papin, Bertrand Favier, Yohan Roulland, Defne Dalkara, Mehmet Ozturk, ALi Hamiche, Stefan Dimitrov, Kiran Padmanabhan
H3.3 is a histone variant, which marks transcription start sites as well as telomeres and heterochromatic sites on the genome. H3.3 presence is thought to positively correlate with transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B combined with short hairpin RNAs against H3.3A, we essentially depleted all H3.3 gene expression in mouse embryonic fibroblasts. Following nearly complete loss of H3.3 in cells, our transcriptomic analyses show very little impact on global gene expression as well as on histone variant H2A...
February 1, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28176872/genotoxic-effects-of-culture-media-on-human-pluripotent-stem-cells
#6
Megha Prakash Bangalore, Syama Adhikarla, Odity Mukherjee, Mitradas M Panicker
Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28171866/selective-biological-responses-of-phagocytes-and-lungs-to-purified-histones
#7
Fatemeh Fattahi, Jamison J Grailer, Hope Lu, Rachel S Dick, Michella Parlett, Firas S Zetoune, Gabriel Nuñez, Peter A Ward
Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B...
February 8, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#8
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28163185/genomic-characterization-and-dynamic-methylation-of-promoter-facilitates-transcriptional-regulation-of-h2a-variants-h2a-1-and-h2a-2-in-various-pathophysiological-states-of-hepatocyte
#9
Monica Tyagi, Divya Reddy, Sanjay Gupta
Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28160502/deubiquitinating-enzyme-usp22-positively-regulates-c-myc-stability-and-tumorigenic-activity-in-mammalian-and-breast-cancer-cells
#10
Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28151037/differential-deposition-of-h2a-z-in-rice-seedling-tissue-during-the-day-night-cycle
#11
Kang Zhang, Wenying Xu, Chunchao Wang, Xin Yi, Zhen Su
Chromatin structure has an important role in modulating gene expression. The incorporation of histone variants into the nucleosome leads to important changes in the chromatin structure. The histone variant H2A.Z is highly conserved between different species of fungi, animals, and plants. However, dynamic changes to H2A.Z in rice have been reported during the day-night cycle. In this study, we generated genome wide maps of H2A.Z for day and night time harvested seedling tissues by combining chromatin immunoprecipitation and high-throughput sequencing...
February 2, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28144029/variants-of-core-histones-and-their-roles-in-cell-fate-decisions-development-and-cancer
#12
REVIEW
Marcus Buschbeck, Sandra B Hake
Histone variants endow chromatin with unique properties and show a specific genomic distribution that is regulated by specific deposition and removal machineries. These variants - in particular, H2A.Z, macroH2A and H3.3 - have important roles in early embryonic development, and they regulate the lineage commitment of stem cells, as well as the converse process of somatic cell reprogramming to pluripotency. Recent progress has also shed light on how mutations, transcriptional deregulation and changes in the deposition machineries of histone variants affect the process of tumorigenesis...
February 1, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28139057/synthesis-of-ubiquitylated-histone-h3-using-a-thiirane-linker-for-chemical-ligation
#13
Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Isao Suetake
Post-translational modifications of histone proteins, which form nucleosome cores, play an important role in gene regulation. Ubiquitin modification is one such modification. We previously reported on the use of a thiirane linker to introduce a 1,2-aminothiol moiety at a cysteine residue for native chemical ligation with peptide thioesters, which permitted isopeptide mimetics to be produced. In this report, we describe the preparation of the ubiquitylated full length histone H3 at the 18 position and the construction of tetranucleosomes with recombinant histones H2A, H2B, H4, and DNA, which are slightly more stable than those that are prepared without ubiquitin modification...
January 31, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28128545/single-molecule-investigations-on-histone-h2a-h2b-dynamics-in-the-nucleosome
#14
Jaehyoun Lee, Tae-Hee Lee
Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28127258/tnf-%C3%AE-sensitizes-chemotherapy-and-radiotherapy-against-breast-cancer-cells
#15
Xiao Wu, Meng-Yao Wu, Min Jiang, Qiaoming Zhi, Xiaojie Bian, Meng-Dan Xu, Fei-Ran Gong, Juan Hou, Min Tao, Liu-Mei Shou, Weiming Duan, Kai Chen, Meng Shen, Wei Li
PURPOSE: Despite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28123501/identification-of-the-molecular-mechanisms-underlying-dilated-cardiomyopathy-via-bioinformatic-analysis-of-gene-expression-profiles
#16
Hu Zhang, Zhuo Yu, Jianchao He, Baotong Hua, Guiming Zhang
In the present study, gene expression profiles of patients with dilated cardiomyopathy (DCM) were re-analyzed with bioinformatics tools to investigate the molecular mechanisms underlying DCM. Gene expression dataset GSE3585 was downloaded from Gene Expression Omnibus, which included seven heart biopsy samples obtained from patients with DCM and five healthy controls. Differential analysis was performed using a Limma package in R to screen for differentially expressed genes (DEGs). Functional enrichment analysis was subsequently conducted for DEGs using the Database for Annotation, Visualization and Integration Discovery...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28112428/specific-glutamic-acid-residues-in-targeted-proteins-induce-exaggerated-retardations-in-phos-tag-sds-page-migration
#17
Eiji Kinoshita, Emiko Kinoshita-Kikuta, Kiyonobu Karata, Toshiki Kawano, Atsuhiro Nishiyama, Morihisa Yamato, Tohru Koike
We describe two unique proteins, Escherichia coli ClpX and human histone H2A, that show extremely retarded migrations relative to their molecular weights in Phos-tag SDS-PAGE, despite being nonphosphorylated. Although ClpX separated into multiple migration bands in Phos-tag gels, the separation was not due to phosphorylation. The N-terminal 47-61 region of ClpX was responsible for producing multiple phosphorylation-independent structural variants, even under denaturing conditions, and some of these variants were detected as highly up-shifted bands...
January 23, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28098861/triptolide-inhibits-viability-and-induces-apoptosis-in-liver-cancer-cells-through-activation-of-the-tumor-suppressor-gene-p53
#18
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...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098859/dna-damage-response-defect-in-williams-beuren-syndrome
#19
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...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#20
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
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