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https://www.readbyqxmd.com/read/29786770/the-extract-of-leonurus-sibiricus-transgenic-roots-with-atpap1-transcriptional-factor-induces-apoptosis-via-dna-damage-and-down-regulation-of-selected-epigenetic-factors-in-human-cancer-cells
#1
Przemysław Sitarek, Tomasz Kowalczyk, Simona Santangelo, Adam J Białas, Monika Toma, Joanna Wieczfinska, Tomasz Śliwiński, Ewa Skała
The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels...
May 21, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29786745/histone-modifications-in-fatty-acid-synthase-modulated-by-carbohydrate-responsive-element-binding-protein-are-associated-with-non%C3%A2-alcoholic-fatty-liver-disease
#2
Can Cai, Huihong Yu, Guangming Huang, Xuan Du, Xiaoqing Yu, Youping Zhou, Wei Shen
Non‑alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and is closely associated with diabetes; however, its pathogenesis remains to be elucidated. Carbohydrate responsive element binding protein (ChREBP), the hub of glucolipid metabolism, regulates the induction of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, by directly binding to carbohydrate response element (ChoRE) in its promoter. Investigations of histone modifications on NAFLD remain in their infancy...
May 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786660/molecular-targets-of-active-anticancer-compounds-derived-from-marine-sources
#3
REVIEW
Xiaoping Song, Ying Xiong, Xin Qi, Wei Tang, Jiajia Dai, Qianqun Gu, Jing Li
Over the past decades, a number of novel compounds, which are produced in the marine environment, have been found to exhibit the anticancer effects. This review focuses on molecular targets of marine-derived anticancer candidates in clinical and preclinical studies. They are kinases, transcription factors, histone deacetylase, the ubiquitin-proteasome system, and so on. Specific emphasis of this review paper is to provide information on the optimization of new target compounds for future research and development of anticancer drugs, based on the identification of structures of these target molecules and parallel compounds...
May 22, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29785653/valproic-acid-treatment-response-in-vitro-is-determined-by-tp53-status-in-medulloblastoma
#4
Bruna Mascaro-Cordeiro, Indhira Dias Oliveira, Francine Tesser-Gamba, Lorena Favaro Pavon, Nasjla Saba-Silva, Sergio Cavalheiro, Patrícia Dastoli, Silvia Regina Caminada Toledo
PURPOSE: Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. METHODS: Dose-response curve determined IC50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments...
May 22, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29785231/advantages-of-evaluating-%C3%AE-h2ax-induction-in-non-clinical-drug-development
#5
REVIEW
Shigeki Motoyama, Akira Takeiri, Kenji Tanaka, Asako Harada, Kaori Matsuzaki, Junko Taketo, Saori Matsuo, Etsuko Fujii, Masayuki Mishima
γH2AX, the phosphorylated form of a histone variant H2AX at Ser 139, is already widely used as a biomarker to research the fundamental biology of DNA damage and repair and to assess the risk of environmental chemicals, pollutants, radiation, and so on. It is also beginning to be used in the early non-clinical stage of pharmaceutical drug development as an in vitro tool for screening and for mechanistic studies on genotoxicity. Here, we review the available information on γH2AX-based test systems that can be used to develop drugs and present our own experience of practically applying these systems during the non-clinical phase of drug development...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/29785087/transcriptomic-impacts-of-rumen-epithelium-induced-by-butyrate-infusion-in-dairy-cattle-in-dry-period
#6
Ransom L Baldwin, Robert W Li, Yankai Jia, Cong-Jun Li
The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function...
2018: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/29785056/genome-wide-mapping-reveals-that-deoxyuridine-is-enriched-in-the-human-centromeric-dna
#7
Xiaoting Shu, Menghao Liu, Zhike Lu, Chenxu Zhu, Haowei Meng, Sihao Huang, Xiaoxue Zhang, Chengqi Yi
Uracil in DNA can be generated by cytosine deamination or dUMP misincorporation; however, its distribution in the human genome is poorly understood. Here we present a selective labeling and pull-down technology for genome-wide uracil profiling and identify thousands of uracil peaks in three different human cell lines. Surprisingly, uracil is highly enriched at the centromere of the human genome. Using mass spectrometry, we demonstrate that human centromeric DNA contains a higher level of uracil. We also directly verify the presence of uracil within two centromeric uracil peaks on chromosomes 6 and 11...
May 21, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29785026/resetting-the-epigenetic-balance-of-polycomb-and-compass-function-at-enhancers-for-cancer-therapy
#8
Lu Wang, Zibo Zhao, Patrick A Ozark, Damiano Fantini, Stacy A Marshall, Emily J Rendleman, Kira A Cozzolino, Nundia Louis, Xingyao He, Marc A Morgan, Yoh-Hei Takahashi, Clayton K Collings, Edwin R Smith, Panagiotis Ntziachristos, Jeffrey N Savas, Lihua Zou, Rintaro Hashizume, Joshua J Meeks, Ali Shilatifard
The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784888/identification-of-brain-metastasis-genes-and-therapeutic-evaluation-of-histone-deacetylase-inhibitors-in-a-clinically-relevant-model-of-breast-cancer-brain-metastasis
#9
Soo-Hyun Kim, Richard P Redvers, Lap Hing Chi, Xiawei Ling, Andrew J Lucke, Robert C Reid, David P Fairlie, Ana Carolina Baptista Moreno Martin, Robin L Anderson, Delphine Denoyer, Normand Pouliot
Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours...
May 21, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#10
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784816/encephalitis-is-mediated-by-rop18-of-toxoplasma-gondii-a-severe-pathogen-in-aids-patients
#11
Ran An, Yuewen Tang, Lijian Chen, Haijian Cai, De-Hua Lai, Kang Liu, Lijuan Wan, Linli Gong, Li Yu, Qingli Luo, Jilong Shen, Zhao-Rong Lun, Francisco J Ayala, Jian Du
The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784800/epigenetic-switch-from-repressive-to-permissive-chromatin-in-response-to-cold-stress
#12
Junghoon Park, Chae Jin Lim, Mingzhe Shen, Hee Jin Park, Joon-Yung Cha, Elisa Iniesto, Vicente Rubio, Tesfaye Mengiste, Jian-Kang Zhu, Ray A Bressan, Sang Yeol Lee, Byeong-Ha Lee, Jing Bo Jin, Jose M Pardo, Woe-Yeon Kim, Dae-Jin Yun
Switching from repressed to active status in chromatin regulation is part of the critical responses that plants deploy to survive in an ever-changing environment. We previously reported that HOS15, a WD40-repeat protein, is involved in histone deacetylation and cold tolerance in Arabidopsis However, it remained unknown how HOS15 regulates cold responsive genes to affect cold tolerance. Here, we show that HOS15 interacts with histone deacetylase 2C (HD2C) and both proteins together associate with the promoters of cold-responsive COR genes, COR15A and COR47 Cold induced HD2C degradation is mediated by the CULLIN4 (CUL4)-based E3 ubiquitin ligase complex in which HOS15 acts as a substrate receptor...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784772/a-heterochromatin-domain-forms-gradually-at-a-new-telomere-and-is-dynamic-at-stable-telomeres
#13
Jinyu Wang, Jessica R Eisenstatt, Julien Audry, Kristen Cornelius, Matthew Shaughnessy, Kathleen L Berkner, Kurt W Runge
Heterochromatin domains play important roles in chromosome biology, organismal development and aging, including centromere function, mammalian female X-chromosome inactivation and senescence-associated heterochromatin foci. In the fission yeast Schizosaccharomyces pombe and metazoans, heterochromatin contains histone H3 that is dimethylated at lysine 9. While factors required for heterochromatin have been identified, the dynamics of heterochromatin formation are poorly understood. Telomeres convert adjacent chromatin into heterochromatin...
May 21, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29784770/tlr-activated-repression-of-fe-s-cluster-biogenesis-drives-a-metabolic-shift-and-alters-histone-and-tubulin-acetylation
#14
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29784032/metabolic-recoding-of-epigenetics-in-cancer
#15
REVIEW
Yi-Ping Wang, Qun-Ying Lei
Dysregulation of metabolism allows tumor cells to generate needed building blocks as well as to modulate epigenetic marks to support cancer initiation and progression. Cancer-induced metabolic changes alter the epigenetic landscape, especially modifications on histones and DNA, thereby promoting malignant transformation, adaptation to inadequate nutrition, and metastasis. Recent advances in cancer metabolism shed light on how aberrations in metabolites and metabolic enzymes modify epigenetic programs. The metabolism-induced recoding of epigenetics in cancer depends strongly on nutrient availability for tumor cells...
May 21, 2018: Cancer communications
https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#16
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29782940/defining-osteoblast-and-adipocyte-lineages-in-the-bone-marrow
#17
J L Pierce, D L Begun, J J Westendorf, M E McGee-Lawrence
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29782855/role-of-statins-and-mevalonate-pathway-on-impaired-hdac2-activity-induced-by-oxidative-stress-in-human-airway-epithelial-cells
#18
Maria Gabriella Matera, Luigino Calzetta, Giulia Gritti, Laura Gallo, Brunella Perfetto, Giovanna Donnarumma, Mario Cazzola, Paola Rogliani, Maria Donniacuo, Barbara Rinaldi
In patients with chronic obstructive pulmonary disease (COPD) the inflammatory response is often steroid-resistant, likely since oxidative stress and cigarette smoking impair histone deacetylase 2 (HDAC2) activity. Since it has been demonstrated that statins may restore the HDAC2 activity in cultured human endothelial cells, the aim of this study was to investigate the effects of statins in reversing the steroid-resistance induced by oxidative stress. We evaluated the effects of simvastatin and dexamethasone on HDAC2 expression and activity, and the role of mevalonate and Rho/ROCK pathways in A549 cells, a human lung type II epithelial cell line stressed with H2 O2 ...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782850/histone-deacetylase-1-promotes-glioblastoma-cell-proliferation-and-invasion-via-activation-of-pi3k-akt-and-mek-erk-signaling-pathways
#19
Shun Li, Xiangrong Chen, Lifang Mao, Kashif Rafiq Zahid, Jun Wen, Liu Zhang, Maoying Zhang, Junwei Duan, Jie Duan, Xiaohong Yin, Yuanchuan Wang, Long Zhao, Xiaoping Tang, Xiangyu Wang, Guozheng Xu
Histone deacetylase 1 (HDAC1) plays a crucial role in cancer progression and development. This enzyme has been confirmed to be a key regulator of tumor biology functions, such as tumor cell proliferation, migration and invasion. However, HDAC1 expression in glioma remains controversial, and its specific function and molecular mechanism in glioblastoma is poorly understood. In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively...
May 18, 2018: Brain Research
https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#20
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
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