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https://www.readbyqxmd.com/read/28433418/binge-alcohol-alters-pnpla3-levels-in-liver-through-epigenetic-mechanism-involving-histone-h3-acetylation
#1
REVIEW
Ricardo J Restrepo, Robert W Lim, Ronald J Korthuis, Shivendra D Shukla
The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for a protein which is highly expressed in adipose tissue and liver, and is implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous to functional lipolytic proteins, the regulation of its tissue expression is reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in humans has been linked to increased susceptibility to alcoholic liver disease. We have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA expression as well as the association of its gene promoter with acetylated histone H3K9 by chromatin immunoprecipitation (ChIP) assay in rat hepatocytes in vitro, and in vivo in mouse and rat models of acute binge, chronic, and chronic followed by acute binge ethanol administration...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28422646/coordinated-control-of-terminal-differentiation-and-restriction-of-cellular-plasticity
#2
Tulsi Patel, Oliver Hobert
The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal differentiation to define the structural and functional properties of a neuron. To study restriction of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE-1 results in activation of ASE neuron type-specific effector genes...
April 19, 2017: ELife
https://www.readbyqxmd.com/read/28420001/nicotinamide-n-methyltransferase-suppression-participates-in-nickel-induced-histone-h3-lysine9-dimethylation-in-beas-2b-cells
#3
Qian Li, Min-Di He, Lin Mao, Xue Wang, Yu-Lin Jiang, Min Li, Yong-Hui Lu, Zheng-Ping Yu, Zhou Zhou
BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 μM NiCl2 for different time periods...
April 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419930/design-synthesis-and-anticancer-potential-of-nsc-319745-hydroxamic-acid-derivatives-as-dnmt-and-hdac-inhibitors
#4
Zigao Yuan, Qinsheng Sun, Dan Li, Shuangshuang Miao, Shaopeng Chen, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418019/live-imaging-of-h3k9-acetylation-in-plant-cells
#5
Kazuki Kurita, Takuya Sakamoto, Noriyoshi Yagi, Yuki Sakamoto, Akihiro Ito, Norikazu Nishino, Kaori Sako, Minoru Yoshida, Hiroshi Kimura, Motoaki Seki, Sachihiro Matsunaga
Proper regulation of histone acetylation is important in development and cellular responses to environmental stimuli. However, the dynamics of histone acetylation at the single-cell level remains poorly understood. Here we established a transgenic plant cell line to track histone H3 lysine 9 acetylation (H3K9ac) with a modification-specific intracellular antibody (mintbody). The H3K9ac-specific mintbody fused to the enhanced green fluorescent protein (H3K9ac-mintbody-GFP) was introduced into tobacco BY-2 cells...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#6
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414096/lysine-specific-demethylase-1-lsd1-depletion-disrupts-monogenic-and-monoallelic-odorant-receptor-or-expression-in-an-olfactory-neuronal-cell-line
#7
Rutesh Vyas, Diane Meredith, Robert P Lane
Function of the mammalian olfactory system depends on specialized olfactory sensory neurons (OSNs) that each express only one allele ("monoallelic") of one odorant receptor (OR) gene ("monogenic"). The lysine-specific demethylase-1 (LSD1) protein removes activating H3K4 or silencing H3K9 methylation marks in a variety of developmental contexts, and is thought to be important for proper OR regulation. Most of the focus in the field has been on a potential "activating" function for LSD1; e.g., in the demethylation of H3K9 associated with the expressed OR allele...
April 13, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28414027/arsenic-activates-the-expression-of-3%C3%AE-hsd-in-mouse-leydig-cells-through-repression-of-histone-h3k9-methylation
#8
Ambreen Alamdar, Guochen Xi, Qingyu Huang, Meiping Tian, Syed Ali Musstjab Akber Shah Eqani, Heqing Shen
Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated...
April 13, 2017: Toxicology and Applied Pharmacology
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
#9
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/28407004/epigenetically-repressing-human-cytomegalovirus-lytic-infection-and-reactivation-from-latency-in-thp-1-model-by-targeting-h3k9-and-h3k27-histone-demethylases
#10
Xin Gan, Haifeng Wang, Yanyan Yu, Wei Yi, Shanshan Zhu, En Li, Yu Liang
Human Cytomegalovirus (hCMV) infects a broad range of the population and establishes life-long latency in the infected individuals. Periodically the latently infected virus can reactivate and becomes a significant cause of morbidity and mortality in immunocompromised individuals. In latent infection, the viral genome is suppressed in a heterochromatic state and viral gene transcription is silenced. Upon reactivation, the repressive chromatin is remodeled to an active form, allowing viral lytic gene transcription, initiated by the expression of viral Immediate Early (IE) genes...
2017: PloS One
https://www.readbyqxmd.com/read/28400174/jmj24-antagonizes-histone-h3k9-demethylase-ibm1-jmj25-function-and-interacts-with-rnai-pathways-for-gene-silencing
#11
Laure Audonnet, Yuan Shen, Dao-Xiu Zhou
Dimethylation of histone H3 lysine 9 (H3K9me2) is a heterochromatic mark linked to DNA methylation and gene repression. Removal of H3K9me2 from gene bodies by the jmjC histone demethylase IBM1/JMJ25 inhibits DNA methylation and derepresses gene expression. In this work, we analyzed the function of a closely related homolog of IBM1/JMJ25, namely JMJ24. We show that jmj24 mutations produced a number of subtle developmental defects, while affecting only a relatively small number of genes at the vegetative stage...
April 8, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28393332/cocaine-administration-and-its-withdrawal-enhance-the-expression-of-genes-encoding-histone-modifying-enzymes-and-histone-acetylation-in-the-rat-prefrontal-cortex
#12
Anna Sadakierska-Chudy, Małgorzata Frankowska, Joanna Jastrzębska, Karolina Wydra, Joanna Miszkiel, Marek Sanak, Małgorzata Filip
Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex...
April 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#13
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 5, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28368536/transcription-factor-crem-mediates-high-glucose-response-in-cardiomyocytes-and-in-a-male-mouse-model-of-prolonged-hyperglycemia
#14
Saviana A Barbati, Claudia Colussi, Lorenza Bacci, Aurora Aiello, Agnese Re, Egidio Stigliano, Andrea M Isidori, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Carlo Gaetano, Simona Nanni
This study aims at investigating the epigenetic landscape of cardiomyocytes exposed to long elevated glucose levels in vitro and in vivo Exposure of mouse HL-1 and rat differentiated H9C2 cardiomyocyte cell lines to high glucose (30 mM) for 72 hours determined some epigenetic changes including upregulation of class I and III HDAC protein levels and activity, inhibition of histone acetylase p300 activity, increase in histone H3 lysine (K) 27 trimethylation (H3K27me3) and reduction in H3K9 acetylation (H3K9Ac)...
March 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28364391/histone-deacetylase-2-inhibition-attenuates-downregulation-of-hippocampal-plasticity-gene-expression-during-aging
#15
Padmanabh Singh, M K Thakur
The brain undergoes several anatomical, biochemical, and molecular changes during aging, which subsequently result in downregulation of synaptic plasticity genes and decline of memory. However, the regulation of these genes during aging is not clearly understood. Previously, we reported that the expression of histone deacetylase (HDAC)2 was upregulated in the hippocampus of old mice and negatively correlated with the decline in recognition memory. As HDAC2 regulates key synaptic plasticity neuronal immediate early genes (IEGs), we have examined their expression and epigenetic regulation...
March 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28361889/the-histone-h3k9-methyltransferase-suv39h-links-sirt1-repression-to-myocardial-infarction
#16
Guang Yang, Xinyu Weng, Yuhao Zhao, Xinjian Zhang, Yuanping Hu, Xin Dai, Peng Liang, Peng Wang, LeiLei Ma, Xiaolei Sun, Lei Hou, Huihui Xu, Mingming Fang, Yuehua Li, Thomas Jenuwein, Yong Xu, Aijun Sun
Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection. SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure. Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation...
March 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28361100/a-novel-de-novo-frameshift-deletion-in-ehmt1-in-a-patient-with-kleefstra-syndrome-results-in-decreased-h3k9-dimethylation
#17
Patrick R Blackburn, Monique Williams, Margot A Cousin, Nicole J Boczek, Geoffrey J Beek, Gwen A Lomberk, Raul A Urrutia, Dusica Babovic-Vuksanovic, Eric W Klee
BACKGROUND: Kleefstra Syndrome (KS) (MIM# 610253) is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 (EHMT1, GLP). EHMT1 (MIM# 607001) encodes a histone methyltransferase that heterodimerizes with EHMT2 (also known as G9a, MIM# 604599), which together are responsible for mono- and dimethylation of H3 lysine 9 (H3K9me1 and -me2), resulting in transcriptional repression of target genes. METHODS: This report describes an 18-year-old woman with intellectual disability, severely limited speech, hypotonia, microcephaly, and facial dysmorphisms, who was found to have a novel de novo single-base frameshift deletion in EHMT1...
March 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28348226/err%C3%AE-induces-h3k9-demethylation-by-lsd1-to-promote-cell-invasion
#18
Julie Carnesecchi, Christelle Forcet, Ling Zhang, Violaine Tribollet, Bruno Barenton, Rafik Boudra, Catherine Cerutti, Isabelle M L Billas, Aurélien A Sérandour, Jason S Carroll, Claude Beaudoin, Jean-Marc Vanacker
Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS)...
March 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28344766/phosphorylation-of-lsd1-by-plk1-promotes-its-chromatin-release-during-mitosis
#19
Bin Peng, Ruifeng Shi, Weiwei Jiang, Yue-He Ding, Meng-Qiu Dong, Wei-Guo Zhu, Xingzhi Xu
BACKGROUND: Lysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown. RESULTS: In this report, we found that polo-like kinase 1 (PLK1) directly interacted with LSD1 and phosphorylated LSD1 at Ser-126 . Nocodazole-induced metaphase arrest promoted release of LSD1 from chromatin, and the phosphorylation-defective mutant LSD1 (S126A) failed to dissociate from chromatin upon nocodazole treatment...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28343968/met-2-dependent-h3k9-methylation-suppresses-transgenerational-small-rna-inheritance
#20
Itamar Lev, Uri Seroussi, Hila Gingold, Roberta Bril, Sarit Anava, Oded Rechavi
In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs...
March 21, 2017: Current Biology: CB
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