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https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#1
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29138005/distinct-hypoxic-regulation-of-preadipocyte-factor-1-pref-1-in-preadipocytes-and-mature-adipocytes
#2
Yunwon Moon, Seongyeol Lee, Bongju Park, Hyunsung Park
Preadipocyte factor-1 (Pref-1) is a secretory soluble protein, which exerts pleiotropic effects on maintenance of cancer stem cell characteristics and commitment of mesenchymal stem cell lineages by inhibiting adipogenesis. Observations that obesity renders the microenvironment of adipose tissues hypoxic and that hypoxia inhibits adipogenesis lead us to investigate whether hypoxia increases the expression of anti-adipogenic Pref-1 in preadipocytes, mature adipocytes, and adipose tissues from obese mouse. In 3T3-L1 preadipocytes, hypoxia induces Pref-1 by a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism accompanied by increase in the levels of the active histone mark, acetylated H3K9/14 (H3K9/14Ac)...
November 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29136592/human-sirtuin-3-sirt3-deacetylates-histone-h3-lysine-56-to-promote-nonhomologous-end-joining-repair
#3
Amrita Sengupta, Devyani Haldar
Human sirtuin 3 (SIRT3) is a conserved NAD(+) dependent deacetylase, which functions in important cellular processes including transcription, metabolism, oxidative stress response. It is a robust mitochondrial deacetylase; however, few studies have indicated its nuclear functions. Here we report interaction of SIRT3 with core histones and identified acetylated histone H3 lysine 56 (H3K56ac) as its novel substrate, in addition to known substrates acetylated H4K16 and H3K9. Further, we showed in response to DNA damage SIRT3 localizes to the repair foci colocalizing with γH2AX and nonhomologous end joining (NHEJ) marker p53-binding protein 1 (53BP1)...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29136238/regulation-of-transcriptional-silencing-and-chromodomain-protein-localization-at-centromeric-heterochromatin-by-histone-h3-tyrosine-41-phosphorylation-in-fission-yeast
#4
Bingbing Ren, Hwei Ling Tan, Thi Thuy Trang Nguyen, Ahmed Mahmoud Mohammed Sayed, Ying Li, Yu-Keung Mok, Henry Yang, Ee Sin Chen
Heterochromatin silencing is critical for genomic integrity and cell survival. It is orchestrated by chromodomain (CD)-containing proteins that bind to methylated histone H3 lysine 9 (H3K9me), a hallmark of heterochromatin. Here, we show that phosphorylation of tyrosine 41 (H3Y41p)-a novel histone H3 modification-participates in the regulation of heterochromatin in fission yeast. We show that a loss-of-function mutant of H3Y41 can suppress heterochromatin de-silencing in the centromere and subtelomere repeat regions, suggesting a de-silencing role for H3Y41p on heterochromatin...
November 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29126440/chromatin-organization-changes-during-the-establishment-and-maintenance-of-the-postmitotic-state
#5
Yiqin Ma, Laura Buttitta
BACKGROUND: Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells...
November 10, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29121593/stimulation-of-liver-igf-1-expression-promotes-peak-bone-mass-achievement-in-growing-rats-a-study-with-pomegranate-seed-oil
#6
Deepa Bachagol, Gilbert Stanley Joseph, Govindraj Ellur, Kalpana Patel, Pamisetty Aruna, Monika Mittal, Shyamsundar Pal China, Ravendra Pratap Singh, Kunal Sharan
Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage...
October 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29118980/sirt1-dependent-modulation-of-methylation-and-acetylation-of-histone-h3-on-lysine-9-h3k9-in-the-zygotic-pronuclei-improves-porcine-embryo-development
#7
Katerina Adamkova, Young-Joo Yi, Jaroslav Petr, Tereza Zalmanova, Kristyna Hoskova, Pavla Jelinkova, Jiri Moravec, Milena Kralickova, Miriam Sutovsky, Peter Sutovsky, Jan Nevoral
Background: The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD(+)-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29113726/expression-of-tissue-specific-imprinted-gene-tumor-suppressing-subtransferable-candidate-4-tssc4-is-altered-in-placentae-produced-by-nuclear-transfer-in-cattle
#8
João C T Penteado, Rodolpho J Borduchi, Mariângela B C Maldonado, Juliano R Sangalli, Tiago H C de Bem, Flavio V Meirelles, Daniel R Arnold, Flavia L Lopes
Embryonic and placental development is highly orchestrated by epigenetic processes. Disruptions in normal placental development, commonly observed in pregnancies produced by nuclear transfer, are associated with abnormal gene expression and altered epigenetic regulation of imprinted and vital placental genes. The objective of this study was to evaluate expression and epigenetic regulation of the imprinted gene TSSC4 in cotyledonary and intercotyledonary tissues from day 60 pregnancies produced by embryo transfer (ET), in vitro fertilization (IVF) and nuclear transfer (NT) in cattle...
November 4, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/29109278/coordinated-regulation-of-heterochromatin-inheritance-by-dpb3-dpb4-complex
#9
Haijin He, Yang Li, Qianhua Dong, An-Yun Chang, Feng Gao, Zhongxuan Chi, Min Su, Faben Zhang, Hyoju Ban, Rob Martienssen, Yu-Hang Chen, Fei Li
During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29105395/the-effect-of-vitrification-on-expression-and-histone-marks-of-igf2-and-oct4-in-blastocysts-cultured-from-two-cell-mouse-embryos
#10
Maryam Jahangiri, Maryam Shahhoseini, Bahar Movaghar
OBJECTIVES: Vitrification is increasingly used in assisted reproductive technology (ART) laboratories worldwide. In this study the effect of vitrification on the expression and modifications of H3 histones of Igf2 and Oct4 was investigated in blastocysts cultured from vitrified and non-vitrified two-cell embryos. MATERIALS AND METHODS: In this experimental study, two-cell embryos were cultured in KSOM medium to reach the blastocyst stage. Expression of Igf2 and Oct4 and modifications of H3 histones in regulatory regions of both genes were compared with in vivo blastocysts, which comprise the control group...
January 2018: Cell Journal
https://www.readbyqxmd.com/read/29101221/%C3%AE-actin-dependent-global-chromatin-organization-and-gene-expression-programs-control-cellular-identity
#11
Xin Xie, Bader Almuzzaini, Nizar Drou, Stephan Kremb, Ayman Yousif, Ann-Kristin Östlund Farrants, Kristin Gunsalus, Piergiorgio Percipalle
During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts from a β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3-lysine-(K)9...
November 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29100410/chidamide-and-decitabine-can-synergistically-induce-apoptosis-of-hodgkin-lymphoma-cells-by-up-regulating-the-expression-of-pu-1-and-klf4
#12
Tao Jiang, Fujue Wang, Lianjie Hu, Xiaomin Cheng, Yuhuan Zheng, Ting Liu, Yongqian Jia
Epigenetic abnormalities play important roles in the pathogenesis of Hodgkin lymphoma (HL). Highly expressed class I histone acetyltransferase (HDAC) and hyper-methylation of the promoter region of tumor suppressor genes have been demonstrated in Hodgkin lymphoma. In this paper, we investigated the synergistic effects of combination treatment of chidamide, a selective HDAC inhibitor, and decitabine, a demethylation agent, for HL cell lines and explored a new strategy for treating HL. The apoptosis rates, cell cycle, mitochondrial transmembrane potentials, epigenetic changes and gene expression of HL cell lines treated with chidamide as a single agent and in combination with decitabine were tested...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098329/linking-site-specific-loss-of-histone-acetylation-to-repression-of-gene-expression-by-the-mycotoxin-ochratoxin-a
#13
Elisabeth Limbeck, Jens T Vanselow, Julian Hofmann, Andreas Schlosser, Angela Mally
Ochratoxin A (OTA) is a potent renal carcinogen but its mechanism has not been fully resolved. In vitro and in vivo gene expression studies consistently revealed down-regulation of gene expression as the predominant transcriptional response to OTA. Based on the importance of specific histone acetylation marks in regulating gene transcription and our recent finding that OTA inhibits histone acetyltransferases (HATs), leading to loss of acetylation of histones and non-histone proteins, we hypothesized that OTA-mediated repression of gene expression may be causally linked to HAT inhibition and loss of histone acetylation...
November 2, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29078403/induction-of-h3k9me3-and-dna-methylation-by-tethered-heterochromatin-factors-in-neurospora-crassa
#14
Jordan D Gessaman, Eric U Selker
Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29077881/interplay-among-h3k9-editing-enzymes-suv39h1-jmjd2c-and-src-1-drives-p66shc-transcription-and-vascular-oxidative-stress-in-obesity
#15
Sarah Costantino, Francesco Paneni, Agostino Virdis, Shafaat Hussain, Shafeeq Ahmed Mohammed, Giuliana Capretti, Alexander Akhmedov, Kevin Dalgaard, Sergio Chiandotto, J Andrew Pospisilik, Thomas Jenuwein, Marco Giorgio, Massimo Volpe, Stefano Taddei, Thomas F Lüscher, Francesco Cosentino
Aims: Accumulation of reactive oxygen species (ROS) promotes vascular disease in obesity, but the underlying molecular mechanisms remain poorly understood. The adaptor p66Shc is emerging as a key molecule responsible for ROS generation and vascular damage. This study investigates whether epigenetic regulation of p66Shc contributes to obesity-related vascular disease. Methods and results: ROS-driven endothelial dysfunction was observed in visceral fat arteries (VFAs) isolated from obese subjects when compared with normal weight controls...
October 25, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29072299/reversing-ski-smad4-mediated-suppression-is-essential-for-th17-cell-differentiation
#16
Song Zhang, Motoki Takaku, Liyun Zou, Ai-di Gu, Wei-Chun Chou, Ge Zhang, Bing Wu, Qing Kong, Seddon Y Thomas, Jonathan S Serody, Xian Chen, Xiaojiang Xu, Paul A Wade, Donald N Cook, Jenny P Y Ting, Yisong Y Wan
T helper 17 (TH17) cells are critically involved in host defence, inflammation, and autoimmunity. Transforming growth factor β (TGFβ) is instrumental in TH17 cell differentiation by cooperating with interleukin-6 (refs 6, 7). Yet, the mechanism by which TGFβ enables TH17 cell differentiation remains elusive. Here we reveal that TGFβ enables TH17 cell differentiation by reversing SKI-SMAD4-mediated suppression of the expression of the retinoic acid receptor (RAR)-related orphan receptor γt (RORγt). We found that, unlike wild-type T cells, SMAD4-deficient T cells differentiate into TH17 cells in the absence of TGFβ signalling in a RORγt-dependent manner...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29054929/mitogen-and-stress-activated-protein-kinase-1-is-required-for-gonadotropin-releasing-hormone-mediated-activation-of-gonadotropin-%C3%AE-subunit-expression
#17
Majd Haj, Andrea Wijeweera, Sergei Rudnizky, Jack Taunton, Lilach Pnueli, Philippa Melamed
Pituitary gonadotropin hormones are regulated by gonadotropin-releasing hormone (GnRH) via MAPK signaling pathways which stimulate gene transcription of the common α-subunit (Cga) and the hormone-specific β-subunits of gonadotropin. We have reported previously that GnRH-induced activities at these genes include various histone modifications, but we did not examine histone phosphorylation. This modification adds a negative charge to residues of the histone tails that interact with the negatively charged DNA, is associated with closed chromatin during mitosis, but is increased at certain genes for transcriptional activation...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29053336/interplay-between-ezh2-and-g9a-regulates-cxcl10-gene-repression-in-idiopathic-pulmonary-fibrosis
#18
William R Coward, Oliver J Brand, Alice Pasini, Gisli Jenkins, Alan J Knox, Linhua Pang
Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodelling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. This study explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases, Enhancer of Zest Homolog 2 (EZH2) and G9a, in CXCL10 repression in IPF. By applying chromatin immunoprecipitation (ChIP), Re-ChIP and proximity ligation assays, we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated H3K27me3 was significantly enriched at the CXCL10 promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from non-fibrotic lungs (F-NL) and that EZH2 and G9a physically interacted with each other...
October 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29049850/-epigenetic-control-of-early-neurodegenerative-events-in-diabetic-retinopathy-by-the-histone-deacetylase-sirt6
#19
María A Zorrilla-Zubilete, Ada Yeste, Francisco J Quintana, Debra Toiber, Raul Mostoslavsky, Dafne M Silberman
Diabetic retinopathy (DR) is one of the common complications associated with diabetes mellitus (DM) and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose-induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard to diagnose at early stages. SIRT6, a NAD-dependent sirtuin deacylase, modulates aging, energy metabolism and neurodegeneration...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29042680/sperm-borne-mir-449b-influences-cleavage-epigenetic-reprogramming-and-apoptosis-of-scnt-embryos-in-bovine
#20
Mengyun Wang, Yang Gao, Pengxiang Qu, Suzhu Qing, Fang Qiao, Yong Zhang, Jesse Mager, Yongsheng Wang
Accumulating evidence indicates the absence of paternally derived miRNAs, piwiRNAs, and proteins may be one important factor contributing to developmental failure in somatic cell cloned embryos. In the present study, we found microRNA-449b (miR-449b) was highly expressed in sperm. Target gene predictions and experimental verification indicate that several embryonic development-related genes, including CDK6, c-MYC, HDAC1 and BCL-2, are targets of miR-449b. We therefore investigated the role of miR-449b using somatic cell nuclear transfer (SCNT) embryo model...
October 17, 2017: Scientific Reports
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