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https://www.readbyqxmd.com/read/29351209/the-prognostic-significance-of-histone-demethylase-utx-in-esophageal-squamous-cell-carcinoma
#1
Shau-Hsuan Li, Hung-I Lu, Wan-Ting Huang, Wan-Yu Tien, Ya-Chun Lan, Wei-Che Lin, Hsin-Ting Tsai, Chang-Han Chen
The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was performed in 106 ESCC patients, and correlated with clinicopathological features and survival. The functional role of UTX in ESCC cells was determined by UTX-mediated siRNA. Univariate analyses showed that high UTX expression was associated with superior overall survival (OS, p = 0...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350772/arsenite-induced-histone-h3-modification-and-its-effects-on-egr1-and-fos-expression-in-hela-cells
#2
Toshihide Suzuki, Hiroshi Watanabe, Kayoko Kita, Taro Honma, Takafumi Ochi
It is evident that trivalent arsenicals do not have mutagenicity, but they are human carcinogens. Recently, epigenetic modification has been considered as one of the important causes of arsenical carcinogenicity. Here we examined global histone H3 modification by trivalent inorganic arsenite (iAs(III)) and its contribution to gene expression in HeLa cells. iAs(III) induced histone H3K9 dimethylation (H3K9me2) and trimethylation (H3K9me3), histone H3S10 phosphorylation (H3S10p), histone H3T11 phosphorylation (H3T11p) and histone H3K9S10 trimethyl-phosphorylation (H3K9me3S10p)...
January 19, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#3
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348808/dual-nampt-hdac-inhibitors-as-a-new-strategy-for-multitargeting-antitumor-drug-discovery
#4
Wei Chen, Guoqiang Dong, Ying Wu, Wannian Zhang, Chaoyu Miao, Chunquan Sheng
Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) inhibitors were designed by a pharmacophore fusion approach. The thiazolocarboxamide inhibitors were highly active for both targets. In particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new strategy for multitarget antitumor drug discovery by simultaneously acting on cancer metabolism and epigenetics.
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#5
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348610/the-histone-methyltransferase-dot1l-inhibits-osteoclastogenesis-and-protects-against-osteoporosis
#6
Yanpan Gao, Wei Ge
Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL-induced RAW264.7 macrophage cells as an osteoclast differentiation model, we found that DOT1L and H3K79me2 levels were upregulated during osteoclast differentiation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348483/cell-type-specific-survey-of-epigenetic-modifications-by-tandem-chromatin-immunoprecipitation-sequencing
#7
Mari Mito, Mitsutaka Kadota, Kaori Tanaka, Yasuhide Furuta, Kuniya Abe, Shintaro Iwasaki, Shinichi Nakagawa
The nervous system of higher eukaryotes is composed of numerous types of neurons and glia that together orchestrate complex neuronal responses. However, this complex pool of cells typically poses analytical challenges in investigating gene expression profiles and their epigenetic basis for specific cell types. Here, we developed a novel method that enables cell type-specific analyses of epigenetic modifications using tandem chromatin immunoprecipitation sequencing (tChIP-Seq). FLAG-tagged histone H2B, a constitutive chromatin component, was first expressed in Camk2a-positive pyramidal cortical neurons and used to purify chromatin in a cell type-specific manner...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348431/a-synthetic-combinatorial-approach-to-disabling-deviant-hedgehog-signaling
#8
C-W Fan, N Yarravarapu, H Shi, O Kulak, J Kim, C Chen, L Lum
Mutations in components of the Hedgehog (HH) signal transduction pathway are found in the majority of basal cell carcinoma (BCC) and medulloblastoma incidents. Cancerous cells with intrinsic or acquired resistance to antagonists targeting the seven transmembrane effector Smoothened (SMO) frequently invoke alternative mechanisms for maintaining deviant activity of the GLI DNA binding proteins. Here we introduce a chemical agent that simultaneously achieves inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC) family...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348366/structures-of-human-prc2-with-its-cofactors-aebp2-and-jarid2
#9
Vignesh Kasinath, Marco Faini, Simon Poepsel, Dvir Reif, Xinyu Ashlee Feng, Goran Stjepanovic, Ruedi Aebersold, Eva Nogales
Transcriptionally repressive histone H3K27 methylation by PRC2 (Polycomb repressive complex 2) is essential for cellular differentiation and development. Here we report cryo-EM structures of human PRC2 in two distinct, active states, while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, while AEBP2 interacts with the RBAP48 subunit mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348326/symmetry-from-asymmetry-or-asymmetry-from-symmetry
#10
Elizabeth W Kahney, Rajesh Ranjan, Ryan J Gleason, Xin Chen
The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29348240/snf1-related-kinase1-controlled-c-s1-bzip-signaling-activates-alternative-mitochondrial-metabolic-pathways-to-ensure-plant-survival-in-extended-darkness
#11
Lorenzo Pedrotti, Christoph Weiste, Thomas Nägele, Elmar Wolf, Francesca Lorenzin, Katrin Dietrich, Andrea Mair, Wolfram Weckwerth, Markus Teige, Elena Baena-González, Wolfgang Dröge-Laser
Sustaining energy homeostasis is of pivotal importance for all living organisms. In Arabidopsis thaliana, evolutionarily conserved SnRK1 kinases (Snf1-RELATED KINASE1) control metabolic adaptation during low energy stress. To unravel starvation-induced transcriptional mechanisms, we performed transcriptome studies of inducible knock-down lines and found that S1-basic leucine Zipper transcription factors (S1-bZIPs) control a defined subset of genes downstream of SnRK1. For example, S1-bZIPs coordinate the expression of genes involved in branched-chain amino acid catabolism, which constitutes an alternative mitochondrial respiratory pathway that is crucial for plant survival during starvation...
January 18, 2018: Plant Cell
https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#12
Kathrin Arndt, Andrea Kranz, Juliane Fohgrub, Adrien Jolly, Anita S Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A Francis Stewart, Claudia Waskow
The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd1a in adult long-term (LT)-HSCs is compatible with adult life and has little effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However, SETD1A-deficient LT-HSCs lose their transcriptional cellular identity accompanied by loss of their proliferative capacity and stem cell function under replicative stress in situ and after transplantation...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#13
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346574/systematic-genetic-interaction-studies-identify-histone-demethylase-utx-as-potential-target-for-ameliorating-huntington-s-disease
#14
Wan Song, Nóra Zsindely, Anikó Faragó, J Lawrence Marsh, László Bodai
No abstract text is available yet for this article.
January 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29345920/acetylation-by-eis-and-deacetylation-by-rv1151c-of-mycobacterium-tuberculosis-hupb-biochemical-and-structural-insight
#15
Keith D Green, Tapan Biswas, Allan H Pang, Melisa J Willby, Matthew S Reed, Olga Stuchlik, Jan Pohl, James E Posey, Oleg V Tsodikov, Sylvie Garneau-Tsodikova
Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. We report biochemical and structural aspects of acetylation of HupB by Eis. We also found that the SirT-family NAD+-dependent deacetylase Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation kinetics...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29344672/histone-deacetylase-inhibitor-trichostatin-a-and-autophagy-inhibitor-chloroquine-synergistically-exert-anti-tumor-activity-in-h-ras-transformed-breast-epithelial-cells
#16
Liang Gao, Xin Sun, Qi Zhang, Xiaochen Chen, Tongwei Zhao, Liqing Lu, Jianbin Zhang, Yupeng Hong
Histone deacetylase inhibitors (HDACIs) cause oncogene‑transformed mammalian cell death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1) and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is involved in HDACI‑mediated oncogene‑transformed mammalian cell death remains unclear. In the present study, H‑ras transformed MCF10A cells were used to investigate the role of FOXO1 in this pathway. Results showed that trichostatin A (TSA), a HDACI, activated apoptosis in MCF10A‑ras cells, but not in MCF10A cells...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#17
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29344279/positive-expression-of-smyd2-is-associated-with-poor-prognosis-in-patients-with-primary-hepatocellular-carcinoma
#18
Shan-Ru Zuo, Xiao-Cong Zuo, Yang He, Wei-Jin Fang, Chun-Jiang Wang, Heng Zou, Pan Chen, Ling-Fei Huang, Li-Hua Huang, Hong Xiang, Shi-Kun Liu
Purpose: SET and MYND domain-containing protein2 (SMYD2), a histone lysine methyltransferases, is a candidate human oncogene in multiple tumors. However, the expression dynamics of SMYD2 in hepatocellular carcinoma (HCC) and its clinical/prognostic significance are unclear. Methods: The SMYD2 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) in HCC tissues and matched adjacent non-tumorous tissues. SMYD2 was silenced in HCC cell lines to determine its role in tumor proliferation and cell cycle progression, and the possible mechanism...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344236/alterations-in-expression-levels-of-genes-in-p53-related-pathways-determined-using-rna-seq-analysis-in-patients-with-breast-cancer-following-cik-therapy
#19
Zuowei Hu, Xiaoye Zhang, Hang Yang, Shuanglai Qin, Yaqi Liu, Wei Xiong, Bing Yuan, Liping Li, Weiqi Yao, Dongcheng Wu
The present study aimed at investigating the underlying molecular mechanisms for patients following cytokine-induced killer (CIK) therapy, particularly involving the alterations in p53-associated signaling pathways, to elucidate whether CIK therapy serves a function in cancer treatment. Samples of blood were collected from patients with breast cancer prior to and following CIK therapy. Two group samples were used for RNA sequencing (RNA-Seq) to determine the alterations in gene expression levels following CIK therapy and one for the quantitative polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344124/molecular-biological-characterization-and-drug-sensitivity-of-chidamide-resistant-non-small-cell-lung-cancer-cells
#20
Song'e Luo, Kai Ma, Hongxia Zhu, Shuren Wang, Mei Liu, Weina Zhang, Shufang Liang, Ningzhi Xu
Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical trials for various types of hematological and solid tumors. Although acquired resistance is common in chemotherapy, the mechanism of resistance to chidamide is poorly characterized. The goal of the present study was to explore, in detail, the mechanism for the induced resistance to chidamide, and investigate a potential cross-resistance to other chemotherapeutic drugs. A549 cells were exposed to gradually increasing chidamide concentrations to establish a chidamide-resistant non-small cell lung cancer cell line (A549-CHI-R)...
December 2017: Oncology Letters
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