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https://www.readbyqxmd.com/read/29352283/using-a-model-comparison-approach-to-describe-the-assembly-pathway-for-histone-h1
#1
Carlos Contreras, Minaya Villasana, Michael J Hendzel, Gustavo Carrero
Histones H1 or linker histones are highly dynamic proteins that diffuse throughout the cell nucleus and associate with chromatin (DNA and associated proteins). This binding interaction of histone H1 with the chromatin is thought to regulate chromatin organization and DNA accessibility to transcription factors and has been proven to involve a kinetic process characterized by a population that associates weakly with chromatin and rapidly dissociates and another population that resides at a binding site for up to several minutes before dissociating...
2018: PloS One
https://www.readbyqxmd.com/read/29352168/epigenetic-control-of-influenza-virus-role-of-h3k79-methylation-in-interferon-induced-antiviral-response
#2
Laura Marcos-Villar, Juan Díaz-Colunga, Juan Sandoval, Noelia Zamarreño, Sara Landeras-Bueno, Manel Esteller, Ana Falcón, Amelia Nieto
Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352142/fbxl10-contributes-to-the-development-of-diffuse-large-b-cell-lymphoma-by-epigenetically-enhancing-erk1-2-signaling-pathway
#3
Xiujuan Zhao, Xing Wang, Qian Li, Wanbiao Chen, Na Zhang, Yu Kong, Junqiang Lv, Lei Cao, Dan Lin, Xi Wang, Guogang Xu, Xudong Wu
Epigenetic modifiers have emerged as critical factors governing the biology of different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an important member of Polycomb repressive complexes, is overexpressed in human diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines. Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL cells abrogates tumor growth in mouse xenograft models...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352129/molecular-characterization-of-the-grape-seeds-extract-s-effect-against-chemically-induced-liver-cancer-in-vivo-and-in-vitro-analyses
#4
Alaaeldin Ahmed Hamza, Gehan Hussein Heeba, Hanan Mohamed Elwy, Chandraprabha Murali, Raafat El-Awady, Amr Amin
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352077/whole-genome-sequencing-of-suppressor-dna-mixtures-identifies-pathways-that-compensate-for-chromosome-segregation-defects-in-schizosaccharomyces-pombe
#5
Xingya Xu, Li Wang, Mitsuhiro Yanagida
Suppressor screening is a powerful method to identify genes that when mutated, rescue the temperature sensitivity of the original mutation. Previously, however, identification of suppressor mutations has been technically difficult. Due to the small genome size of Schizosaccharomyces pombe, we developed a spontaneous suppressor screening technique, followed by a cost-effective sequencing method. Genomic DNAs of 10 revertants which survived at the restrictive temperature of the original temperature sensitive (ts) mutant were mixed together as one sample before constructing a library for sequencing...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29352018/oncohistones-drivers-of-pediatric-cancers
#6
REVIEW
Faizaan Mohammad, Kristian Helin
One of the most striking results in the area of chromatin and cancer in recent years has been the identification of recurrent mutations in histone genes in pediatric cancers. These mutations occur at high frequency and lead to the expression of mutant histones that exhibit oncogenic features. Thus, they are termed oncohistones. Thus far, mutations have been found in the genes encoding histone H3 and its variants. The expression of the oncohistones affects the global chromatin landscape through mechanisms that have just begun to be unraveled...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29351847/phosphorylation-of-ezh2-by-ampk-suppresses-prc2-methyltransferase-activity-and-oncogenic-function
#7
Lixin Wan, Kexin Xu, Yongkun Wei, Jinfang Zhang, Tao Han, Christopher Fry, Zhao Zhang, Yao Vickie Wang, Liyu Huang, Min Yuan, Weiya Xia, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Jinsong Liu, Yun Wu, Victor X Jin, Xiangpeng Dai, Jianfeng Guo, Jia Liu, Shulong Jiang, Jin Li, John M Asara, Myles Brown, Mien-Chie Hung, Wenyi Wei
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351836/interrogating-interactions-and-modifications-of-histones-in-live-cells
#8
Xiao-Meng Li, Xiang David Li
In this issue of Cell Chemical Biology, new methods are reported to interrogate histone interactions and modifications. Kleiner et al. (2018) develop a chemical proteomics platform for profiling of direct, context-dependent histone-protein interactions in living cells, and Delachat et al. (2018) engineer fluorescent sensors for coexisting histone modifications in live stem cells.
January 18, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29351814/setdb1-prevents-tet2-dependent-activation-of-iap-retroelements-in-na%C3%A3-ve-embryonic-stem-cells
#9
Özgen Deniz, Lorenzo de la Rica, Kevin C L Cheng, Dominik Spensberger, Miguel R Branco
BACKGROUND: Endogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET-dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos...
January 19, 2018: Genome Biology
https://www.readbyqxmd.com/read/29351209/the-prognostic-significance-of-histone-demethylase-utx-in-esophageal-squamous-cell-carcinoma
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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