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active DNA demethylation

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https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#1
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29135280/factors-affecting-mouse-somatic-cell-nuclear-reprogramming-by-rabbit-ooplasms
#2
Xia Huang, Lili Song, Zhiyan Zhan, Haihui Gu, Haizhong Feng, Yanxin Li
Successful development of interspecies somatic cell nuclear transfer (iSCNT) embryos depends on compatibilities between ooplasmic and nuclear components. However, the mechanisms by which the compatibilities are regulated are still unknown. In this study, using mouse Oct4-green fluorescent protein (GFP) cells as donors and rabbit oocytes as recipients, we show that Oct4 and other pluripotency related genes were reactivated in some of mouse-rabbit iSCNT embryos, which could also activate Oct4 promoter-driven GFP reporter gene expression...
November 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/29126272/generation-of-alloantigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#3
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation, and graft-versus-host disease (GVHD) in hematopoietic stem-cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
November 4, 2017: International Immunology
https://www.readbyqxmd.com/read/29116071/-crispr-cas9-editing-based-modeling-of-hypoxia-in-renal-cancer-cells
#4
N A Zhigalova, S V Zhenilo, A V Artemov, E B Prokhortchouk
Uncontrolled growth in the cell mass of malignant tumors induces intensive angiogenesis. However, the demands of the cancer cells for nutrients and oxygen remain only partially met. Hypoxia is a process that accompanies malignant transformation and evokes changes in the DNA methylation profile in solid tumors. To a certain extent, these changes, including the hypermethylation of tumor suppressor gene promoters, are related to the decrease in the activity of Tet proteins under the conditions of oxygen and free radical deficit...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29108636/dynamic-expression-of-tet1-tet2-and-tet3-dioxygenases-in-mouse-and-human-placentas-throughout-gestation
#5
Joanna Rakoczy, Nisha Padmanabhan, Ada M Krzak, Jens Kieckbusch, Tereza Cindrova-Davies, Erica D Watson
INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function...
November 2017: Placenta
https://www.readbyqxmd.com/read/29106571/retrieval-induced-upregulation-of-tet3-in-pyramidal-neurons-of-the-dorsal-hippocampus-mediates-cocaine-associated-memory-reconsolidation
#6
Cao Liu, Xue Sun, Zhilin Wang, Qiumin Le, Peipei Liu, Changyou Jiang, Feifei Wang, Lan Ma
Background: Memory retrieval refers to re-exposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods: We used cocaine-induced conditioned place preference (CPP) to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dHC...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29102482/vitamin-c-a-new-player-in-regulation-of-the-cancer-epigenome
#7
REVIEW
Linn Gillberg, Andreas D Ørskov, Minmin Liu, Laurine B S Harsløf, Peter A Jones, Kirsten Grønbæk
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care...
November 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29100355/role-of-dna-methylation-in-perinatal-nicotine-induced-development-of-heart-ischemia-sensitive-phenotype-in-rat-offspring
#8
Jun Ke, Nianguo Dong, Lei Wang, Yong Li, Chiranjib Dasgupta, Lubo Zhang, Daliao Xiao
Background and purpose: Maternal cigarette smoking increases the risk of cardiovascular disease in offspring. Recently, we have demonstrated that perinatal nicotine exposure alters heart development and increases heart susceptibility to ischemia/reperfusion (I/R) injury in rat offspring. The present study tested the hypothesis that DNA methylation plays a key role in the nicotine-induced development of heart ischemia-sensitive phenotype in offspring. Experimental approach: Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from gestational day 4 until postnatal day 10...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100015/an-endosirna-based-repression-mechanism-counteracts-transposon-activation-during-global-dna-demethylation-in-embryonic-stem-cells
#9
Rebecca V Berrens, Simon Andrews, Dominik Spensberger, Fátima Santos, Wendy Dean, Poppy Gould, Jafar Sharif, Nelly Olova, Tamir Chandra, Haruhiko Koseki, Ferdinand von Meyenn, Wolf Reik
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29097205/characterization-of-human-alkb-homolog-1-produced-in-mammalian-cells-and-demonstration-of-mitochondrial-dysfunction-in-alkbh1-deficient-cells
#10
Tina A Müller, Sarah L Struble, Katheryn Meek, Robert P Hausinger
Alkbh1 is a mammalian homolog of the Escherichia coli DNA repair enzyme AlkB, an Fe(II) and 2-oxoglutarate dependent dioxygenase that removes alkyl lesions from DNA bases. The human homolog ALKBH1 has been associated with six different enzymatic activities including DNA, mRNA, or tRNA hydroxylation, cleavage at abasic (AP) sites in DNA, as well as demethylation of histones. The reported cellular roles of this protein reflect the diverse enzymatic activities and include direct DNA repair, tRNA modification, and histone modification...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29094436/low-level-perfluorooctanoic-acid-enhances-3%C3%A2-t3-l1-preadipocyte-differentiation-via-altering-peroxisome-proliferator-activated-receptor-gamma-expression-and-its-promoter-dna-methylation
#11
Yue Ma, Jie Yang, Yanjian Wan, Yang Peng, Shuai Ding, Yuanyuan Li, Bing Xu, Xi Chen, Wei Xia, Yuebin Ke, Shunqing Xu
Recent studies suggest that perfluorooctanoic acid (PFOA) can play a role in the development of obesity; however, the associated mechanisms are poorly understood. We investigated how PFOA exposure affected the differentiation of 3 T3-L1 preadipocytes and the associated transcriptional and epigenetic mechanisms. Cells treated with different doses of PFOA (ranging from 0.01 to 100 μg ml(-1) ) were assessed for proliferation, differentiation and triglyceride accumulation. The gene expression levels of peroxisome proliferator activated receptor gamma (PPARγ) and its target genes were measured...
November 2, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29091409/cucurbit-7-uril-driven-host-guest-chemistry-for-reversible-intervention-of-5-formylcytosine-targeted-biochemical-reactions
#12
Shao-Ru Wang, Yan-Yan Song, Lai Wei, Chao-Xing Liu, Bo-Shi Fu, Jia-Qi Wang, Xi-Ran Yang, Yi-Nong Liu, Si-Min Liu, Tian Tian, Xiang Zhou
The 5-formylcytosine (5fC) is identified as one of key players in active DNA demethylation and also an epigenetic mark in mammals, thus representing a novel attractive target to chemical intervention. The current study represents an attempt to develop a reversible 5fC-targeted intervention tool. A supramolecular aldehyde reactive probe was therefore introduced for selective conversion of the 5fC to 5fC-AD nucleotide. Using various methods, we demonstrate that, the cucurbit[7]uril (CB7) selectively targets the 5fC-AD nucleotide in DNA, however, the binding of CB7 to 5fC-AD does not affect the hydrogen bonding properties of natural nucleobases in duplex DNA...
November 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29078035/dual-control-of-ros1-mediated-active-dna-demethylation-by-the-dna-damage-binding-protein-2-ddb2
#13
Dolores Córdoba-Cañero, Valérie Cognat, Rafael R Ariza, Teresa Roldán Arjona, Jean Molinier
DNA methylation contributes to key regulatory processes during plant development by controlling gene expression. Genomic methylation patterns are dynamic and must be properly maintained and/or re-established upon DNA replication and active removal, therefore requiring sophisticated control mechanisms. Here, we identified a direct interplay between the DNA repair factor DNA DAMAGE BINDING protein 2 (DDB2) and the ROS1-mediated active DNA demethylation pathway in Arabidopsis thaliana. We showed that DDB2 forms a complex with ROS1 and AGO4 and that they act at ROS1 locus to modulate DNA methylation levels and therefore ROS1 expression...
October 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29070695/relationship-between-dna-methylation-in-the-5-cpg-island-of-the-slc47a1-mate1-gene-and-inter-individual-variability-in-mate1-expression-in-the-human-liver
#14
Toshihiro Tanaka, Takeshi Hirota, Ichiro Ieiri
Multidrug and toxin extrusion protein 1 (MATE1), which is encoded by SLC47A1, mediates the excretion of organic cations into bile and urine. Some genetic variants in human MATE1 altered its transport function in in vitro experiments; however, differences in the pharmacokinetics of substrate drugs cannot be explained by genetic variations in humans. In the present study, we investigated whether DNA methylation was involved in inter-individual variability in MATE1 expression in the human liver. Approximately 20-fold inter-individual variability in MATE1 mRNA expression levels was observed in liver samples and mRNA expression levels negatively correlated with methylation levels of the CpG island in the 27 kb upstream of SLC47A1 DNA demethylation by a treatment with 5-aza-2'-deoxycytidine increased MATE1 mRNA expression in MATE1-negative cell lines...
October 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29066026/cd4-cd28-kir-cd11a-hi-t-cells-correlate-with-disease-activity-and-are-characterized-by-a-pro-inflammatory-epigenetic-and-transcriptional-profile-in-lupus-patients
#15
Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M Strickland, Nathan C Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D Wren, Pei-Suen Tsou, Emily E Lewis, Kathleen Maksimowicz-McKinnon, W Joseph McCune, Bruce C Richardson, Amr H Sawalha
OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus. METHODS: The size of the CD4+CD28+KIR+CD11a(hi) T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a(hi) T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29054852/selective-base-excision-repair-of-dna-damage-by-the-non-base-flipping-dna-glycosylase-alkc
#16
Rongxin Shi, Elwood A Mullins, Xing-Xing Shen, Kori T Lay, Philip K Yuen, Sheila S David, Antonis Rokas, Brandt F Eichman
DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA)...
October 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#17
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29042941/epigallocatechin-gallate-inhibits-the-growth-and-promotes-the-apoptosis-of-bladder-cancer-cells
#18
Chenchen Feng, Yatfaat Ho, Chuanyu Sun, Guowei Xia, Qiang Ding, Bin Gu
Epigallocatechin gallate (EGCG) has been revealed to inhibit the proliferation and induce the apoptosis of several types of tumor, in addition to inhibiting DNA methyltransferase activity, leading to CpG demethylation. Tissue factor pathway inhibitor 2 (TFPI-2) expression is downregulated in bladder cancer. The present study revealed that this downregulation was partly due to hypermethylation of the TFPI-2 gene promoter, which was decreased by EGCG treatment. In addition, the present study demonstrated that EGCG could inhibit the viability and invasion, and induce the apoptosis, of bladder cancer T24 cells...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29039788/impact-of-natural-compounds-on-dna-methylation-levels-of-the-tumor-suppressor-gene-rassf1a-in-cancer
#19
REVIEW
Reinhard H Dammann, Antje M Richter, Adriana P Jiménez, Michelle Woods, Miriam Küster, Chamindri Witharana
Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in the pathogenesis of human cancer. This silencing is accomplished by aberrant chromatin modifications including DNA hypermethylation of the gene promoter. One of the most frequently hypermethylated TSG in human cancer is the Ras Association Domain Family 1A (RASSF1A) gene. Aberrant methylation of RASSF1A has been reported in melanoma, sarcoma and carcinoma of different tissues. RASSF1A hypermethylation has been correlated with tumor progression and poor prognosis...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29036586/epigenetic-mechanisms-underlie-the-crosstalk-between-growth-factors-and-a-steroid-hormone
#20
Yehoshua Enuka, Morris E Feldman, Animesh Chowdhury, Swati Srivastava, Moshit Lindzen, Aldema Sas-Chen, Renaud Massart, David Cheishvili, Matthew J Suderman, Yoav Zaltsman, Chiara A Mazza, Kirti Shukla, Cindy Körner, Noa Furth, Mattia Lauriola, Moshe Oren, Stefan Wiemann, Moshe Szyf, Yosef Yarden
Crosstalk between growth factors (GFs) and steroid hormones recurs in embryogenesis and is co-opted in pathology, but underlying mechanisms remain elusive. Our data from mammary cells imply that the crosstalk between the epidermal GF and glucocorticoids (GCs) involves transcription factors like p53 and NF-κB, along with reduced pausing and traveling of RNA polymerase II (RNAPII) at both promoters and bodies of GF-inducible genes. Essentially, GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal inhibitory loops...
September 28, 2017: Nucleic Acids Research
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