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De novo DNA Methylation

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https://www.readbyqxmd.com/read/29147493/the-effect-of-the-ovarian-varicose-vein-on-the-dna-methylation-in-the-rat-s-oocyte
#1
Amirhossein Mohammadi, Bagher Minaei Zangi, Mahshid Delfan Azari, Rafieh Alizadeh, Mohammad Salehi, Erfan Daneshi, Mohammad Jafar Rezaei, Mehdi Abbasi
Objectives: We intended to determine whether the ovarian varicose which is one of the common etiologies of the pelvic congestion syndrome, has the ability to interfere with the DNA methylation reprogramming in the oocyte and thereby affect the oocyte quality or not. Materials and Methods: Varicose model was induced according to the Turner's method in the rats. Briefly, a 20-gauge needle was placed on the left renal vein and a thread was tied over both the needle and the renal vein medial to the insertion of the ovarian vein, and then the needle was removed...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29133799/hit-and-run-epigenetic-editing-prevents-senescence-entry-in-primary-breast-cells-from-healthy-donors
#2
Emily A Saunderson, Peter Stepper, Jennifer J Gomm, Lily Hoa, Adrienne Morgan, Michael D Allen, J Louise Jones, John G Gribben, Tomasz P Jurkowski, Gabriella Ficz
Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29120020/identification-of-a-mafb-mutation-in-a-patient-with-multicentric-carpotarsal-osteolysis
#3
Lei Zhuang, Sabine Adler, Daniel Aeberli, Peter M Villiger, Beat Trueb
Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant disease of the skeleton characterised by progressive destruction of carpal and tarsal bones. Recently, it has been demonstrated that this disease is caused by heterozygous mutations in the gene for the transcriptional repressor MAFB. We analysed genomic DNA and RNA from leucocytes of a female patient diagnosed with MCTO. We identified the mutation c.161C>T in the genomic sequence and in the expressed messenger RNA for MAFB. This is the second report of the c...
November 9, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29100357/dnmt3b-overexpression-contributes-to-aberrant-dna-methylation-and-myc-driven-tumor-maintenance-in-t-all-and-burkitt-s-lymphoma
#4
Candace J Poole, Wenli Zheng, Atul Lodh, Aleksey Yevtodiyenko, Daniel Liefwalker, Honglin Li, Dean W Felsher, Jan van Riggelen
Aberrant DNA methylation is a hallmark of cancer. However, our understanding of how tumor cell-specific DNA methylation patterns are established and maintained is limited. Here, we report that in T-cell acute lymphoblastic leukemia (T-ALL) and Burkitt's lymphoma the MYC oncogene causes overexpression of DNA methyltransferase (DNMT) 1 and 3B, which contributes to tumor maintenance. By utilizing a tetracycline-regulated MYC transgene in a mouse T-ALL (EμSRα-tTA;tet-o-MYC) and human Burkitt's lymphoma (P493-6) model, we demonstrated that DNMT1 and DNMT3B expression depend on high MYC levels, and that their transcription decreased upon MYC-inactivation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099956/recycling-drug-screen-repurposes-hydroxyurea-as-a-sensitizer-of-glioblastomas-to-temozolomide-targeting-de-novo-dna-synthesis-irrespective-of-molecular-subtype
#5
Jian Teng, Seyedali Hejazi, Lotte Hiddingh, Litia Carvalho, Mark de Gooijer, Hiroaki Wakimoto, Marco Barazas, Marie Tannous, Andrew S Chi, David P Noske, Pieter Wesseling, Thomas Wurdinger, Tracy T Batchelor, Bakhos A Tannous
Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide; TMZ). The five-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through MGMT (O6-methylguanine DNA methyltransferase) promoter methylation status in the tumor...
November 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29078403/induction-of-h3k9me3-and-dna-methylation-by-tethered-heterochromatin-factors-in-neurospora-crassa
#6
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/29074627/isoform-specific-localization-of-dnmt3a-regulates-dna-methylation-fidelity-at-bivalent-cpg-islands
#7
Massimiliano Manzo, Joël Wirz, Christina Ambrosi, Rodrigo Villaseñor, Bernd Roschitzki, Tuncay Baubec
DNA methylation is a prevalent epigenetic modification involved in transcriptional regulation and essential for mammalian development. While the genome-wide distribution of this mark has been studied to great detail, the mechanisms responsible for its correct deposition, as well as the cause for its aberrant localization in cancers, have not been fully elucidated. Here, we have compared the activity of individual DNMT3A isoforms in mouse embryonic stem and neuronal progenitor cells and report that these isoforms differ in their genomic binding and DNA methylation activity at regulatory sites...
October 26, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29074164/defective-regulation-of-l1-endogenous-retroelements-in-primary-sjogren-s-syndrome-and-systemic-lupus-erythematosus-role-of-methylating-enzymes
#8
Clio P Mavragani, Adrianos Nezos, Irina Sagalovskiy, Surya Seshan, Kyriakos A Kirou, Mary K Crow
OBJECTIVE: To investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively...
October 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29072296/embryonic-epigenetic-reprogramming-by-a-pioneer-transcription-factor-in-plants
#9
Zeng Tao, Lisha Shen, Xiaofeng Gu, Yizhong Wang, Hao Yu, Yuehui He
Epigenetic modifications, including chromatin modifications and DNA methylation, have a central role in the regulation of gene expression in plants and animals. The transmission of epigenetic marks is crucial for certain genes to retain cell lineage-specific expression patterns and maintain cell fate. However, the marks that have accumulated at regulatory loci during growth and development or in response to environmental stimuli need to be deleted in gametes or embryos, particularly in organisms such as plants that do not set aside a germ line, to ensure the proper development of offspring...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29069387/functional-role-of-dna-methylation-at-the-flo1-promoter-in-budding-yeast
#10
Kei-Ichi Sugiyama, Hiroko Furusawa, Petr Grúz, Masamitsu Honma
We have previously reported that the transformation of the budding yeast with plasmids encoding the human DNA methyltransferases DNMT1 and DNMT3B cDNAs induce the mRNA of flocculin gene FLO1 and the flocculation phenotype. In the present study, we evaluated the effect of DNMT inhibitor in the transformed yeasts using a FLO1 promoter-based green fluorescent protein (GFP) reporter gene assay. The DNMT inhibitor, 5-aza-2'-deoxycytidine (5AZ), decreased GFP fluorescence driven by FLO1 promoter in DNMT -genes transformed yeast ( DNMT yeast)...
October 24, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29058037/epigenetic-regulation-of-agronomical-traits-in-brassicaceae
#11
REVIEW
Etsuko Itabashi, Kenji Osabe, Ryo Fujimoto, Tomohiro Kakizaki
Epigenetic regulation, covalent modification of DNA and changes in histone proteins are closely linked to plant development and stress response through flexibly altering the chromatin structure to regulate gene expression. In this review, we will illustrate the importance of epigenetic influences by discussing three agriculturally important traits of Brassicaceae. (1) Vernalization, an acceleration of flowering by prolonged cold exposure regulated through epigenetic silencing of a central floral repressor, FLOWERING LOCUS C...
October 20, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/29032247/specifications-of-targeting-heterochromatin-modifications-in-plants
#12
REVIEW
Jered M Wendte, Robert J Schmitz
Plants encode a diverse repertoire of DNA methyltransferases that have specialized to target cytosines for methylation in specific sequence contexts. These include the de novo methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which methylates cytosines in all sequence contexts through an RNA guided process, the CHROMOMETHYLASES (CMTs), which methylate CHH and CHG cytosines (where H is A, T, or C), and the maintenance methyltransferase, METHYLTRANSFERASE 1 (MET1), which maintains methylation of symmetrical CG contexts...
October 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29031013/intragenic-hypomethylation-of-dnmt3a-in-patients-with-myelodysplastic-syndrome
#13
Ying-Ying Zhang, Jing-Dong Zhou, Dong-Qin Yang, Pin-Fang He, Dong-Ming Yao, Zhen Qian, Jing Yang, Wen-Rong Xu, Jiang Lin, Jun Qian
BACKGROUND: DNMT3A is a DNA methyltransferase that acts in de novo methylation. Aberrant expression of DNMT3A has been reported in several human diseases, including myelodysplastic syndrome (MDS). However, the pattern of DNMT3A methylation remains unknown in MDS. METHODS: The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze its clinical significance in MDS...
October 14, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29027601/dnmt1-dnmt3a-and-dnmt3b-proteins-are-differently-expressed-in-mouse-oocytes-and-early-embryos
#14
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
DNA methylation is one of the epigenetic mechanisms and plays important roles during oogenesis and early embryo development in mammals. DNA methylation is basically known as adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. This mechanism is composed of two main processes: de novo methylation and maintenance methylation, both of which are catalyzed by specific DNA methyltransferase (DNMT) enzymes. To date, six different DNMTs have been characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and DNMT3L...
December 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29024628/biologico-clinical-significance-of-dnmt3a-variants-expression-in-acute-myeloid-leukemia
#15
Na Lin, Wei Fu, Chen Zhao, Bixin Li, Xiaojing Yan, Yan Li
DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients...
October 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978023/genomic-alterations-in-mucins-across-cancers
#16
Ryan J King, Fang Yu, Pankaj K Singh
The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976982/role-of-uhrf1-in-de-novo-dna-methylation-in-oocytes-and-maintenance-methylation-in-preimplantation-embryos
#17
Shoji Maenohara, Motoko Unoki, Hidehiro Toh, Hiroaki Ohishi, Jafar Sharif, Haruhiko Koseki, Hiroyuki Sasaki
The methylation of cytosine at CG sites in the mammalian genome is dynamically reprogrammed during gametogenesis and preimplantation development. It was previously shown that oocyte-derived DNMT1 (a maintenance methyltransferase) is essential for maintaining and propagating CG methylation at imprinting control regions in preimplantation embryos. In mammalian somatic cells, hemimethylated-CG-binding protein UHRF1 plays a critical role in maintaining CG methylation by recruiting DNMT1 to hemimethylated CG sites...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28973513/non-random-length-distribution-of-individual-telomeres-in-immunodeficiency-centromeric-instability-and-facial-anomalies-syndrome-type-i
#18
Shira Sagie, Omer Edni, Joseph Weinberg, Shir Toubiana, Tal Kozlovski, Tzviel Frostig, Nirit Katzin, Irit Bar-Am, Sara Selig
Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. While it was demonstrated that the mean telomere length is significantly shorter in ICF type I cells, it is unknown whether all telomeres are equally vulnerable to shortening. To study this question we determined by combined telomere-FISH and spectral karyotyping the relative length of each individual telomere in lymphoblastoid cell lines (LCLs) generated from multiple ICF syndrome patients and control individuals...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28965139/epigenetic-changes-in-preimplantation-embryos-subjected-to-laser-manipulation
#19
Sachin D Honguntikar, Sujith Raj Salian, Fiona D'Souza, Shubhashree Uppangala, Guruprasad Kalthur, Satish Kumar Adiga
The advantage of using laser for assisted hatching in routine assisted reproductive technology (ART) practice is debatable. Recently, it has been shown that laser-manipulated mouse embryos had compromised genetic integrity. However, the impact of laser-assisted hatching (LAH) on the epigenetic integrity of the preimplantation embryos is not elucidated so far. Since continuous thermal stress on embryos was found to lower mRNA levels of de novo (bovine) methyl transferases in embryos, we hypothesize that thermal energy induced during LAH may alter the epigenetic signature through abnormal de novo methyl transferases (Dnmts) levels...
December 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28959968/epigenetic-restriction-of-extraembryonic-lineages-mirrors-the-somatic-transition-to-cancer
#20
Zachary D Smith, Jiantao Shi, Hongcang Gu, Julie Donaghey, Kendell Clement, Davide Cacchiarelli, Andreas Gnirke, Franziska Michor, Alexander Meissner
In mammals, the canonical somatic DNA methylation landscape is established upon specification of the embryo proper and subsequently disrupted within many cancer types. However, the underlying mechanisms that direct this genome-scale transformation remain elusive, with no clear model for its systematic acquisition or potential developmental utility. Here, we analysed global remethylation from the mouse preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions with substantial disruption of bimodal, CpG density-dependent methylation in the placental progenitor...
September 28, 2017: Nature
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