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https://www.readbyqxmd.com/read/28087629/jmjd2c-kdm4c-facilitates-the-assembly-of-essential-enhancer-protein-complexes-at-the-onset-of-embryonic-stem-cell-differentiation
#1
Rute A Tomaz, Jennifer L Harman, Donja Karimlou, Lauren Weavers, Lauriane Fritsch, Tony Bou-Kheir, Emma Bell, Ignacio Del Valle Torres, Kathy K Niakan, Cynthia Fisher, Onkar Joshi, Hendrik G Stunnenberg, Edward Curry, Slimane Ait-Si-Ali, Helle F Jørgensen, Véronique Azuara
Jmjd2/Kdm4 H3K9-demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we uncover that Jmjd2c facilitates this process by stabilizing the assembly of Mediator-Cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28078514/the-molecular-basis-of-the-organization-of-repetitive-dna-containing-constitutive-heterochromatin-in-mammals
#2
REVIEW
Gohei Nishibuchi, Jérôme Déjardin
Constitutive heterochromatin is composed mainly of repetitive elements and represents the typical inert chromatin structure in eukaryotic cells. Approximately half of the mammalian genome is made of repeat sequences, such as satellite DNA, telomeric DNA, and transposable elements. As essential genes are not present in these regions, most of these repeat sequences were considered as junk DNA in the past. However, it is now clear that these regions are essential for chromosome stability and the silencing of neighboring genes...
January 11, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28076698/emerging-role-of-setdb1-as-a-therapeutic-target
#3
Archana Venkataramana Karanth, Radhika Radha Maniswami, Seema Prashanth, Hemalatha Govindaraj, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis. Recent studies indicate that SETDB1 is abnormally expressed in various human cancer conditions which contributed to enhanced tumor growth and metastasis. Hence, SETDB1 appears to be a promising epigenetic target for therapeutic intervention...
January 11, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28067316/long-term-exposure-to-a-safe-dose-of-bisphenol-a-reduced-protein-acetylation-in-adult-rat-testes
#4
Zhuo Chen, Xuezhi Zuo, Dongliang He, Shibin Ding, Fangyi Xu, Huiqin Yang, Xin Jin, Ying Fan, Li Ying, Chong Tian, Chenjiang Ying
Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a 'safe' dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#5
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063010/chaetocin-reactivates-the-lytic-replication-of-epstein-barr-virus-from-latency-via-reactive-oxygen-species
#6
Shilun Zhang, Juan Yin, Jiang Zhong
Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L(-1))...
January 5, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28060835/histone-h3k9-demethylase-jmjd2b-activates-adipogenesis-by-regulating-h3k9-methylation-on-ppar%C3%AE-and-c-ebp%C3%AE-during-adipogenesis
#7
Min-Kyung Jang, Ji-Hyun Kim, Myeong Ho Jung
Previous studies have shown that tri- or di-methylation of histone H3 at lysine 9 (H3K9me3/me2) on the promoter of the peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) contribute to the repression of PPARγ and C/EBPα and inhibition of adipogenesis in 3T3-L1 preadipocytes. The balance of histone methylation is regulated by histone methyltransferases and demethylases. However, it is poorly understood which demethylases are responsible for removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα...
2017: PloS One
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#8
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28056970/inhibition-of-histone-acetylation-by-curcumin-reduces-alcohol-induced-fetal-cardiac-apoptosis
#9
Xiaochen Yan, Bo Pan, Tiewei Lv, Lingjuan Liu, Jing Zhu, Wen Shen, Xupei Huang, Jie Tian
BACKGROUND: Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. METHODS AND RESULTS: Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2...
January 5, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28055238/valproic-acid-increases-histone-acetylation-and-alters-gene-expression-in-the-donor-cells-but-does-not-improve-the-in-vitro-developmental-competence-of-buffalo-bubalus-bubalis-embryos-produced-by-hand-made-cloning
#10
Naresh L Selokar, Monika Saini, Himanshu Agrawal, Prabhat Palta, Manmohan Singh Chauhan, Radheysham Manik, Suresh Kumar Singla
Use of histone deacetylase inhibitors (HDACis) is believed to improve the developmental competence and quality of cloned embryos produced. We examined the effects of treatment of buffalo fibroblasts with valproic acid (VPA), a HDACi on these cells and on embryos produced from them by hand-made cloning. VPA treatment (1.5, 3.0, or 4.5 mM) altered (p < 0.05) the growth characteristics and relative expression level of HDAC1, DNMT1, DNMT3a, P53, and CASPASE3, and the global level of H3K9/14ac, H4K5ac, and H3K18ac but not H3K27me3 in the cells...
January 5, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28051130/the-histone-3-lysine-9-methyltransferase-inhibitor-chaetocin-improves-prognosis-in-a-rat-model-of-high-salt-diet-induced-heart-failure
#11
Tomohiko Ono, Naomi Kamimura, Tomohiro Matsuhashi, Toshihiro Nagai, Takahiko Nishiyama, Jin Endo, Takako Hishiki, Tsuyoshi Nakanishi, Noriaki Shimizu, Hirotoshi Tanaka, Shigeo Ohta, Makoto Suematsu, Masaki Ieda, Motoaki Sano, Keiichi Fukuda, Ruri Kaneda
Histone acetylation has been linked to cardiac hypertrophy and heart failure. However, the pathological implications of changes in histone methylation and the effects of interventions with histone methyltransferase inhibitors for heart failure have not been fully clarified. Here, we focused on H3K9me3 status in the heart and investigated the effects of the histone H3K9 methyltransferase inhibitor chaetocin on prognoses in Dahl salt-sensitive rats, an animal model of chronic heart failure. Chaetocin prolonged survival and restored mitochondrial dysfunction...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28044469/epigenetic-silencing-and-activation-of-transcription-influence-on-the-radiation-sensitivity-of-glioma-cell-lines
#12
A Sak, D Kübler, K Bannik, M Groneberg, S Strunz, R Kriehuber, M Stuschke
PURPOSE: To uncover the role of EZH2 and its opponent ASHL2, a polycomb and trithorax group protein, respectively on the radioresponsiveness of glioma cell lines. MATERIAL AND METHODS: Expression of EZH2 and ASHL2 was inhibited by siRNA in glioma cell lines. The effect on histone methylation, gene expression, DNA damage repair signaling, cell cycle checkpoints, apoptosis and tumor control were evaluated. RESULTS: Inhibition of EZH2 (EZH2i) led to a transcriptional dysregulation with upregulation of 544 and downregulation of 445 genes...
January 3, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28043732/interactions-between-cannabidiol-and-%C3%AE-9-thc-following-acute-and-repeated-dosing-rebound-hyperactivity-sensorimotor-gating-and-epigenetic-and-neuroadaptive-changes-in-the-mesolimbic-pathway
#13
Stephanie M Todd, Cilla Zhou, David J Clarke, Tariq W Chohan, Dilara Bahceci, Jonathon C Arnold
The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation...
December 30, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28028172/histone-deacetylase-1-is-essential-for-rod-photoreceptor-differentiation-by-regulating-acetylation-at-histone-h3-lysine-9-and-histone-h4-lysine-12-in-the-mouse-retina
#14
Renata C Ferreira, Evgenya Y Popova, Jessica James, Marcelo Rs Briones, Samuel S Zhang, Colin J Barnstable
Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas we used a pharmacological approach which showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12), but not lysine 27 of histone 3 (H3K27), and led to maintained expression of progenitor-specific genes such as Vsx2 and Hes1 with concomitant block of expression of rod-specific genes...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28013212/organ-specific-epigenetic-changes-induced-by-the-non-genotoxic-liver-carcinogen-methapyrilene-in-fischer-344-rats
#15
Svitlana Shpyleva, Kostiantyn Dreval, Aline de Conti, Iryna Kindrat, Stepan Melnyk, Jian Yan, Tao Chen, Frederick A Beland, Igor P Pogribny
Continuous lifetime exposure to certain natural and man-made chemicals is a major cause of cancers in humans; therefore, evaluating the carcinogenic risks of chemicals remains important. Currently, substantial progress has been made in identification of genotoxic carcinogens; in contrast, predicting a carcinogenic potential of non-genotoxic compounds is a challenge due to many different modes of action that may lead to tumorigenesis. In the present study, we investigated the effects of the non-genotoxic liver carcinogen methapyrilene and the nongenotoxic non-carcinogen usnic acid at doses that do not exhibit organ cytotoxicity on epigenomic alterations in the liver and kidneys of Fischer 344 (F344) rats...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28007739/ischemic-preconditioning-confers-epigenetic-repression-of-mtor-and-induction-of-autophagy-through-g9a-dependent-h3k9-dimethylation
#16
Olof Gidlöf, Andrea L Johnstone, Kerstin Bader, Bohdan B Khomtchouk, Jiaqi J O'Reilly, Selvi Celik, Derek J Van Booven, Claes Wahlestedt, Bernhard Metzler, David Erlinge
BACKGROUND: Ischemic preconditioning (IPC) protects the heart from prolonged ischemic insult and reperfusion injury through a poorly understood mechanism. Post-translational modifications of histone residues can confer rapid and drastic switches in gene expression in response to various stimuli, including ischemia. The aim of this study was to investigate the effect of histone methylation in the response to cardiac ischemic preconditioning. METHODS AND RESULTS: We used cardiac biopsies from mice subjected to IPC to quantify global levels of 3 of the most well-studied histone methylation marks (H3K9me2, H3K27me3, and H3K4me3) with Western blot and found that H3K9me2 levels were significantly increased in the area at risk compared to remote myocardium...
December 22, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28007596/soft-matrices-downregulate-fak-activity-to-promote-growth-of-tumor-repopulating-cells
#17
Youhua Tan, Adam Richard Wood, Qiong Jia, Wenwen Zhou, Junyu Luo, Fang Yang, Junwei Chen, Junjian Chen, Jian Sun, Jihye Seong, Arash Tajik, Rishi Singh, Ning Wang
Tumor-repopulating cells (TRCs) are a tumorigenic sub-population of cancer cells that drives tumorigenesis. We have recently reported that soft fibrin matrices maintain TRC growth by promoting histone 3 lysine 9 (H3K9) demethylation and Sox2 expression and that Cdc42 expression influences H3K9 methylation. However, the underlying mechanisms of how soft matrices induce H3K9 demethylation remain elusive. Here we find that TRCs exhibit lower focal adhesion kinase (FAK) and H3K9 methylation levels in soft fibrin matrices than control melanoma cells on 2D rigid substrates...
December 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27997534/dna-methylation-signatures-of-the-plant-chromomethyltransferases
#18
Quentin Gouil, David C Baulcombe
DNA methylation in plants is traditionally partitioned into CG, CHG and CHH contexts (with H any nucleotide but G). By investigating DNA methylation patterns in trinucleotide contexts in four angiosperm species, we show that such a representation hides spatial and functional partitioning of different methylation pathways and is incomplete. CG methylation (mCG) is largely context-independent whereas, at CHG motifs, there is under-representation of mCCG in pericentric regions of A. thaliana and tomato and throughout the chromosomes of maize and rice...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27993678/chemical-inhibition-of-the-histone-acetyltransferase-activity-in-arabidopsis-thaliana
#19
Felipe Aquea, Tania Timmermann, Ariel Herrera-Vásquez
Chemical inhibition of chromatin regulators provides an effective approach to investigate the roles of chromatin modifications in plant and animals. In this work, chemical inhibition of the Arabidopsis histone acetyltransferase activity by γ-butyrolactone (MB-3), the inhibitor of the catalytic activity of mammalian GENERAL CONTROL NON-REPRESSIBLE 5 (GCN5) is evaluated. Arabidopsis seedlings were germinated in LS medium supplemented with different concentrations of MB-3, and inhibition in the root length and yellowed leaves were observed...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27984744/survival-in-quiescence-requires-the-euchromatic-deployment-of-clr4-suv39h-by-argonaute-associated-small-rnas
#20
Richard I Joh, Jasbeer S Khanduja, Isabel A Calvo, Meeta Mistry, Christina M Palmieri, Andrej J Savol, Shannan J Ho Sui, Ruslan I Sadreyev, Martin J Aryee, Mo Motamedi
Quiescence (G0) is a ubiquitous stress response through which cells enter reversible dormancy, acquiring distinct properties including reduced metabolism, resistance to stress, and long life. G0 entry involves dramatic changes to chromatin and transcription of cells, but the mechanisms coordinating these processes remain poorly understood. Using the fission yeast, here, we track G0-associated chromatin and transcriptional changes temporally and show that as cells enter G0, their survival and global gene expression programs become increasingly dependent on Clr4/SUV39H, the sole histone H3 lysine 9 (H3K9) methyltransferase, and RNAi proteins...
December 15, 2016: Molecular Cell
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