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https://www.readbyqxmd.com/read/29180474/vitamin-c-sensitizes-melanoma-to-bet-inhibitors
#1
Gaofeng Wang, Sushmita Mustafi, Vladimir Camarena, Claude-Henry Volmar, Tyler C Huff, David W Sant, Shaun P Brothers, Zhao-Jun Liu, Claes Wahlestedt
Bromodomain and extra-terminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in Phase I clinical trials. Here we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi including JQ1, I-BET151, CPI-203, and BI-2536...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29163803/hat1-induces-lung-cancer-cell-apoptosis-via-up-regulating-fas
#2
Na Han, Lei Shi, Qiuyun Guo, Wei Sun, Yang Yu, Li Yang, Xiaoxi Zhang, Mengxian Zhang
The dysfunction of apoptosis is one of the factors contributing to lung cancer (LC) growth. Histone acetyltransferase HAT1 can up regulate cell apoptosis. This study aims to investigate the mechanism by which HAT1 induces LC cell (LCC) apoptosis via up regulating the expression of Fas. In this study, the surgically removed human LC tissues were collected. LCCs were isolated from the LC tissues and analyzed for the expression of HAT1 and Fas by RT-qPCR and Western blotting. We observed that the expression of Fas was negatively correlated with PAR2 in LCCs...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162325/scriptaid-improves-the-reprogramming-of-donor-cells-and-enhances-canine-porcine-interspecies-embryo-development
#3
Jin-Gu No, Tai-Young Hur, Minghui Zhao, Seunghoon Lee, Mi-Kyung Choi, Yoon-Seok Nam, Dong-Hyun Yeom, Gi-Sun Im, Dong-Hoon Kim
Histone methylation, histone acetylation, and DNA methylation are the important factors for somatic cell nuclear transfer (SCNT). Histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been used to improve cloning efficiency. In particular, scriptaid, an HDACi, has been shown to improve SCNT efficiency. However, no studies have been performed on canines. Here, we evaluated the effects of scriptaid on histone modification in canine ear fibroblasts (cEFs) and cloned canine embryos derived from cEFs...
November 18, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/29080998/analysis-of-the-global-regulator-lae1-uncovers-a-connection-between-lae1-and-the-histone-acetyltransferase-hat1-in-fusarium-fujikuroi
#4
Eva-Maria Niehaus, Lena Rindermann, Slavica Janevska, Martin Münsterkötter, Ulrich Güldener, Bettina Tudzynski
The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs), a family of plant hormones. Recent genome sequencing revealed the genetic capacity for the biosynthesis of 46 additional secondary metabolites besides the industrially produced GAs. Among them are the pigments bikaverin and fusarubins, as well as mycotoxins, such as fumonisins, fusarin C, beauvericin, and fusaric acid. However, half of the potential secondary metabolite gene clusters are silent. In recent years, it has been shown that the fungal specific velvet complex is involved in global regulation of secondary metabolism in several filamentous fungi...
October 28, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29064603/histone-deacetylase-inhibitor-stimulates-e2-and-p4-secretion-in-sika-deer-ovarian-granulosa-cells-at-a-moderate-dose
#5
Mingjie Xing, Xiumin Chen, Xiaoxia Li, Yifeng Yang, Xiaoxu Wang, Xinyan Cao, Hailong Xue, Shiyong Wang, Yunfei Diao, Weigang Zhao, Meng Zhao, Xuezhe Cui, Tong Chang, Baozeng Xu, Haijun Wei
The histone deacetylase inhibitor (HDACi) and tumor suppressor play an important role in genome reorganization and epigenetic regulation. In this study, granulosa cells (GCs) isolated from sika deer ovaries were cultured and treated with different concentrations of trichostatin A (TSA) for 48 h. It was found that TSA inhibited GCs proliferation and induced GCs apoptosis by upregulating expression of BAX, meanwhile, downregulating expression of GLUT3, GLUT8, BCL-XL. In addition, TSA caused cell cycle arrest at the G1 and G2/M phase accompanied by reducing expression of Cyclin D2 and CDK4...
October 24, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29059104/transfusion-strategies-are-associated-with-epigenetic-changes-following-blunt-trauma
#6
Martin Sillesen, Yongqing Li, Hasan B Alam
INTRODUCTION: Epigenetics has been identified in multiple diseases. The effect of transfusion strategy on epigenetics is unknown. We hypothesized that expression of epigenetic regulating genes would be associated with resuscitation strategy following blunt trauma. METHODS: Retrospective study using the inflammation in host response to injury (glue grant) dataset. Volume transfused over 24 hours of packed red blood cells (PRBC), Fresh Frozen Plasma(FFP), Platelets(PLT) as well as crystalloids was extracted along with leucocyte microarray data of genes with known epigenetic modulating activity from day 1 after injury...
October 20, 2017: Shock
https://www.readbyqxmd.com/read/28977641/pp32-and-set-taf-i%C3%AE-proteins-regulate-the-acetylation-of-newly-synthesized-histone-h4
#7
Francisco Saavedra, Carlos Rivera, Elizabeth Rivas, Paola Merino, Daniel Garrido, Sergio Hernández, Ignasi Forné, Isabelle Vassias, Zachary A Gurard-Levin, Iván E Alfaro, Axel Imhof, Geneviève Almouzni, Alejandra Loyola
Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28864009/negative-uterine-asynchrony-retards-early-equine-conceptus-development-and-upregulation-of-placental-imprinted-genes
#8
Charlotte Gibson, Marta de Ruijter-Villani, Tom A E Stout
INTRODUCTION: Placental imprinted genes appear to be sensitive indicators of an inappropriate pre-implantation environment. This study examined the effects of negative uterine asynchrony after embryo transfer (ET) on early horse embryo development, and yolk-sac membrane expression of DNA methyltransferases (DNMTs) and equine specific placental imprinted genes. METHODS: Day 8 embryos were transferred to recipient mares on day 8 (synchronous) or day 3 (asynchronous) after ovulation, and conceptuses were recovered 6 or 11 days later (day 14 or 19 of development)...
September 2017: Placenta
https://www.readbyqxmd.com/read/28765096/effects-of-bpa-on-global-dna-methylation-and-global-histone-3-lysine-modifications-in-sh-sy5y-cells-an-epigenetic-mechanism-linking-the-regulation-of-chromatin-modifiying-genes
#9
Mine Senyildiz, Ecem Fatma Karaman, Serap Sancar Bas, Pelin Arda Pirincci, Sibel Ozden
Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the production of polycarbonate plastic and epoxy resins, resulting in high risk on human health. In present study we aimed to investigate the effects of BPA on global and gene specific DNA methylation, global histone modifications and regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH-SY5Y). Cells were treated with BPA at 0.1, 1 and 10μM concentrations for 48 and 96h. IC50 value of BPA was determined as 183 and 129μM in SH-SY5Y cells after 24h by MTT and NRU tests, respectively...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28666830/sophora-subprosrate-polysaccharide-inhibited-cytokine-chemokine-secretion-via-suppression-of-histone-acetylation-modification-and-nf-%C3%AE%C2%BAb-activation-in-pcv2-infected-swine-alveolar-macrophage
#10
Jian Yang, Hong-Lian Tan, Li-Yuan Gu, Man-Ling Song, Yuan-Ying Wu, Jian-Bo Peng, Zong-Bao Lan, Ying-Yi Wei, Ting-Jun Hu
In the present study, effect of Sophora subprosrate polysaccharide on PCV2 infection-induced inflammation and histone acetylation modification in swine alveolar macrophage 3D4/2 cells was described for the first time. The relationship between histone acetylation modifications and inflammation response was investigated. The results showed that PCV2 infection induced inflammation by promoting the secretion of TNF-α, IL-1β, IL-6 and IL-10 in 3D4/2 cells. The production of TNF-α, IL-1β and IL-6 and their mRNA expression levels markedly decreased while the level and mRNA expression of IL-10 were elevated when the cells were treated with Sophora subprosrate polysaccharide...
November 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28666361/identification-of-multiple-roles-for-histone-acetyltransferase-1-in-replication-coupled-chromatin-assembly
#11
Paula A Agudelo Garcia, Michael E Hoover, Pei Zhang, Prabakaran Nagarajan, Michael A Freitas, Mark R Parthun
Histone acetyltransferase 1 (Hat1) catalyzes the acetylation of newly synthesized histone H4 at lysines 5 and 12 that accompanies replication-coupled chromatin assembly. The acetylation of newly synthesized H4 occurs in the cytoplasm and the function of this acetylation is typically ascribed to roles in either histone nuclear import or deposition. Using cell lines from Hat1+/+ and Hat1-/- mouse embryos, we demonstrate that Hat1 is not required for either histone nuclear import or deposition. We employed quantitative proteomics to characterize Hat1-dependent changes in the composition of nascent chromatin structure...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28551908/-involvement-of-epigenetic-regulation-in-cerebral-cell-death-following-traumatic-brain-injury-in-a-rat-model
#12
Mona Shehadeh, Moti Ben-Shabat, Jana Livshits, Eilam Palzur
INTRODUCTION: Traumatic brain injuries (TBI) are a major cause of mortality and disability among young adults. TBI are characterized by primary injury, the result of a mechanical impact to the cranium and a secondary injury, a series of molecular mechanism processes developing thereafter. Cerebral cells modify their gene and protein expression as a result of the injury. Epigenetic modifications have a key role as regulators of gene transcription and may simultaneously be involved in the regulation of the molecular pathways following TBI...
May 2017: Harefuah
https://www.readbyqxmd.com/read/28524020/altered-gene-expression-of-epigenetic-modifying-enzymes-in-response-to-dietary-supplementation-with-linseed-oil
#13
Ran Li, Eveline M Ibeagha-Awemu
Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO...
May 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28486547/hat2-mediates-histone-h4k4-acetylation-and-affects-micrococcal-nuclease-sensitivity-of-chromatin-in-leishmania-donovani
#14
Pravin K Jha, Mohd Imran Khan, Anshul Mishra, Pradeep Das, Kislay K Sinha
Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans...
2017: PloS One
https://www.readbyqxmd.com/read/28480311/strip2-is-indispensable-for-the-onset-of-embryonic-stem-cell-differentiation
#15
Davood Sabour, Sureshkumar Perumal Srinivasan, Susan Rohani, Vilas Wagh, John Antonydas Gaspar, Darius Panek, Mostafa Abootorabi Ardestani, Michael Xavier Doss, Nicole Riet, Hinrich Abken, Jürgen Hescheler, Symeon Papadopoulos, Agapios Sachinidis
The role of striatin interacting protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2-silenced murine (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild-type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for the KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that differentiation of KD ESCs is repressed...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28407860/effects-of-mg132-on-the-in%C3%A2-vitro-development-and-epigenetic-modification-of-debao-porcine-somatic-cell-nuclear-transfer-embryos
#16
Kaiyuan Shen, Xiangping Li, Xiaoli Dai, Ping Wang, Sheng Li, Zhaocheng Xiong, Peifang Chen, Qingyou Liu, Deshun Shi
The present study was undertaken to examine the effect of MG132, a proteasome inhibitor, on the in vitro development, zygotic genome activation (ZGA) and epigenetic modification of Debao porcine somatic cell nuclear transfer (SCNT) embryos. Treatment of oocytes with 1 μM MG132 from 30 h to 42 h of maturation and SCNT embryos with 5 μM MG132 for 2 h after fusion resulted in higher blastocyst yield (36.5%) of SCNT embryos compared with the control group (11.0%). The ZGA of SCNT embryos at 2- and 4-cell stages was also enhanced by MG132 treatment through altering the RNA pol II status and increasing the expression of eIF3A and TFIIA...
May 2017: Theriogenology
https://www.readbyqxmd.com/read/28301168/deletion-of-a-histone-acetyltransferase-leads-to-the-pleiotropic-activation-of-natural-products-in-metarhizium-robertsii
#17
Aili Fan, Wubin Mi, Zhiguo Liu, Guohong Zeng, Peng Zhang, Youcai Hu, Weiguo Fang, Wen-Bing Yin
Histone deacetylation normally decreases the gene expression in organisms. By genome-wide deletions of epigenetic regulators in entomopathogenic fungus Metarhizium robertsii, unexpected activations of orphan secondary metabolite genes have been found upon the disruption of a histone acetyltransferase (HAT) gene Hat1. This led to the characterization of 11 new natural products, including eight isocoumarin derivatives meromusides A-H and two nonribosomal peptides meromutides A and B. Therefore, disruption of HAT represents a new approach to mine chemical diversity from fungi...
April 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28268229/the-hdac-inhibitor-laq824-enhances-epigenetic-reprogramming-and-in-vitro-development-of-porcine-scnt-embryos
#18
Jun-Xue Jin, Sanghoon Lee, Anukul Taweechaipaisankul, Geon A Kim, Byeong Chun Lee
BACKGROUND/AIMS: Hypoacetylation caused by aberrant epigenetic nuclear reprogramming results in low efficiency of mammalian somatic cell nuclear transfer (SCNT). Many epigenetic remodeling drugs have been used in attempts to improve in vitro development of porcine SCNT embryos. In this study, we examined the effects of LAQ824, a structurally novel histone acetylase inhibitor, on the nuclear reprogramming and in vitro development of porcine SCNT embryos. METHODS: LAQ824 treatment was supplemented during the culture of SCNT embryos...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28143904/ampk-promotes-mitochondrial-biogenesis-and-function-by-phosphorylating-the-epigenetic-factors-dnmt1-rbbp7-and-hat1
#19
Traci L Marin, Brendan Gongol, Fan Zhang, Marcy Martin, David A Johnson, Han Xiao, Yinsheng Wang, Shankar Subramaniam, Shu Chien, John Y-J Shyy
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) acts as a master regulator of cellular energy homeostasis by directly phosphorylating metabolic enzymes and nutrient transporters and by indirectly promoting the transactivation of nuclear genes involved in mitochondrial biogenesis and function. We explored the mechanism of AMPK-mediated induction of gene expression. We identified AMPK consensus phosphorylation sequences in three proteins involved in nucleosome remodeling: DNA methyltransferase 1 (DNMT1), retinoblastoma binding protein 7 (RBBP7), and histone acetyltransferase 1 (HAT1)...
January 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/28107582/immunoexpression-of-hdac1-hdac2-and-hat1-in-actinic-cheilitis-and-lip-squamous-cell-carcinoma
#20
E S Chrun, F Modolo, Dsc Vieira, Áls Borges-Júnior, R G Castro, F I Daniel
BACKGROUND: Acetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers...
January 20, 2017: Oral Diseases
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