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De novo DNA Methylation

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https://www.readbyqxmd.com/read/29767839/jak2-v617f-positive-acute-myeloid-leukaemia-aml-a-comparison-between-de-novo-aml-and-secondary-aml-transformed-from-an-underlying-myeloproliferative-neoplasm-a-study-from-the-bone-marrow-pathology-group
#1
Jason Aynardi, Rashmi Manur, Paul R Hess, Seble Chekol, Jennifer J D Morrissette, Daria Babushok, Elizabeth Hexner, Heesun J Rogers, Eric D Hsi, Elizabeth Margolskee, Attilio Orazi, Robert Hasserjian, Adam Bagg
The JAK2 V617F mutation is characteristic of most Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and occurs rarely in de novo acute myeloid leukaemia (AML). We sought to characterize AMLs that harbour this mutation and distinguish those that arise de novo (AML-DN) from those that reflect transformation of an underlying MPN (AML-MPN). Forty-five patients with JAK2 V617F-mutated AML were identified; 15 were AML-DN and 30 were AML-MPN. AML-MPN cases were more likely to have splenomegaly (P = 0·02), MPN-like megakaryocytes and higher mean JAK2 V617F VAF at diagnosis (P = 0·04)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765016/b-cell-activation-and-plasma-cell-differentiation-are-inhibited-by-de-novo-dna-methylation
#2
Benjamin G Barwick, Christopher D Scharer, Ryan J Martinez, Madeline J Price, Alexander N Wein, Robert R Haines, Alexander P R Bally, Jacob E Kohlmeier, Jeremy M Boss
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29748607/mir-455-3p-inhibits-the-degenerate-process-of-chondrogenic-differentiation-through-modification-of-dna-methylation
#3
Hao Sun, Xiaoyi Zhao, Chengyun Zhang, Ziji Zhang, Jiayong Lun, Weiming Liao, Zhiqi Zhang
The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3'-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29740169/gain-of-function-mutations-in-dnmt3a-in-patients-with-paraganglioma
#4
Laura Remacha, Maria Currás-Freixes, Raúl Torres-Ruiz, Francesca Schiavi, Rafael Torres-Pérez, Bruna Calsina, Rocío Letón, Iñaki Comino-Méndez, Juan M Roldán-Romero, Cristina Montero-Conde, María Santos, Lucía Inglada Pérez, Guillermo Pita, María R Alonso, Emiliano Honrado, Susana Pedrinaci, Benedicto Crespo-Facorro, Antonio Percesepe, Maurizio Falcioni, Sandra Rodríguez-Perales, Esther Korpershoek, Santiago Ramón-Maiques, Giuseppe Opocher, Cristina Rodríguez-Antona, Mercedes Robledo, Alberto Cascón
PURPOSE: The high percentage of patients carrying germline mutations makes pheochromocytomas/paragangliomas the most heritable of all tumors. However, there are still cases unexplained by mutations in the known genes. We aimed to identify the genetic cause of disease in patients strongly suspected of having hereditary tumors. METHODS: Whole-exome sequencing was applied to the germlines of a parent-proband trio. Genome-wide methylome analysis, RNA-seq, CRISPR/Cas9 gene editing, and targeted sequencing were also performed...
May 8, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29736015/locus-specific-control-of-the-de-novo-dna-methylation-pathway-in-arabidopsis-by-the-classy-family
#5
Ming Zhou, Ana Marie S Palanca, Julie A Law
DNA methylation is essential for gene regulation, transposon silencing and imprinting. Although the generation of specific DNA methylation patterns is critical for these processes, how methylation is regulated at individual loci remains unclear. Here we show that a family of four putative chromatin remodeling factors, CLASSY (CLSY) 1-4, are required for both locus-specific and global regulation of DNA methylation in Arabidopsis thaliana. Mechanistically, these factors act in connection with RNA polymerase-IV (Pol-IV) to control the production of 24-nucleotide small interfering RNAs (24nt-siRNAs), which guide DNA methylation...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29728652/defective-germline-reprogramming-rewires-the-spermatogonial-transcriptome
#6
Lina Vasiliauskaitė, Rebecca V Berrens, Ivayla Ivanova, Claudia Carrieri, Wolf Reik, Anton J Enright, Dónal O'Carroll
Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia...
May 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29728366/the-hush-complex-cooperates-with-trim28-to-repress-young-retrotransposons-and-new-genes
#7
Luisa Robbez-Masson, Christopher H C Tie, Lucia Conde, Hale Tunbak, Connor Husovsky, Iva A Tchasovnikarova, Richard T Timms, Javier Herrero, Paul J Lehner, Helen M Rowe
Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of a SVA retrotransposon reporter. By using naïve vs. primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development...
May 4, 2018: Genome Research
https://www.readbyqxmd.com/read/29721644/morphology-oriented-epigenetic-research
#8
REVIEW
Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages...
May 2, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29720401/methionine-biosynthesis-and-transport-are-functionally-redundant-for-the-growth-and-virulence-of-salmonella-typhimurium
#9
Asma Ul Husna, Nancy Wang, Simon A Cobbold, Hayley J Newton, Dianna M Hocking, Jonathan J Wilksch, Timothy A Scott, Mark R Davies, Jay C Hinton, Jai J Tree, Trevor Lithgow, Malcolm J McConville, Richard Strugnell
Methionine (Met) is an amino acid essential for many important cellular and biosynthetic functions, including the initiation of protein synthesis and S-adenosylmethionine-mediated methylation of proteins, RNA, and DNA. The de novo biosynthetic pathway of Met is well conserved across prokaryotes but absent from vertebrates, making it a plausible antimicrobial target. Using a systematic approach, we examined the essentiality of de novo methionine biosynthesis in Salmonella enterica serovar Typhimurium, a bacterial pathogen causing significant gastrointestinal and systemic diseases in humans and agricultural animals...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29695701/-detection-of-dna-methylation-by-dnmt3a-methyltransferase-using-methyl-dependent-restriction-endonucleases
#10
A V Sergeev, O V Kirsanova, A G Loiko, E I Nomerotskaya, E S Gromova
DNA methylation at cytosine residues in CpG sites by DNA methyltransferases (MTases) is associated with various cell processes. Eukaryotic MTase Dnmt3a is the key enzyme that establishes the de novo methylation pattern. A new in vitro assay for DNA methylation by murine MTase Dnmt3a was developed using methyl-dependent restriction endonucleases (MD-REs), which specifically cleave methylated DNA. The Dnmt3a catalytic domain (Dnmt3a-CD) was used together with KroI and PcsI MD-REs. The assay consists in consecutive methylation and cleavage of fluorescently labeled DNA substrates, then the reaction products are visualized in polyacrylamide gel to determine the DNA methylation efficiency...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29687201/folate-promotes-s-adenosyl-methionine-reactions-and-the-microbial-methylation-cycle-and-boosts-ruminants-production-and-reproduction
#11
REVIEW
Imtiaz Hussain Raja Abbasi, Farzana Abbasi, Lamei Wang, Mohamed E Abd El Hack, Ayman A Swelum, Ren Hao, Junhu Yao, Yangchun Cao
Folate has gained significant attention due to its vital role in biological methylation and epigenetic machinery. Folate, or vitamin (B9 ), is only produced through a de novo mechanism by plants and micro-organisms in the rumen of mature animals. Although limited research has been conducted on folate in ruminants, it has been noted that ruminal synthesis could not maintain folate levels in high yielding dairy animals. Folate has an essential role in one-carbon metabolism and is a strong antiproliferative agent...
April 23, 2018: AMB Express
https://www.readbyqxmd.com/read/29685765/uv-induced-dna-methyltransferase-1-promotes-hypermethylation-of-tissue-inhibitor-of-metalloproteinase-2-in-the-human-skin
#12
Ha-Young Kim, Dong Hun Lee, Mi Hee Shin, Hye Sun Shin, Min-Kyoung Kim, Jin Ho Chung
BACKGROUND: Ultraviolet (UV) radiation has been reported to influence epigenetic regulation by affecting the expression of genome regulators such as DNA methyltransferase 1 (DNMT1). DNMT1 is a "gene silencer," that is responsible for the maintenance of DNA methylation and contribution to de novo methylation. Implications of DNMT1's involvement in the expression of UV-induced proteins have been previously reported. OBJECTIVE: To investigate for changes in DNA methylation-associated gene expressions by UV and to analyze the role of DNA methylation in the suppression of TIMP2 in UV-irradiated human skin...
March 15, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29676649/asbestos-induces-epigenetic-repression-of-ras-association-domain-containing-protein-1-p16-kinase-4a-inhibitor-and-p14-alternative-reading-frame-in-normal-human-mesothelial-cells
#13
Sichuan Xi, Eden C Payabyab, David M Straughan, Emily S Reardon, Mary Zhang, Julie A Hong, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2 ) for up to 10 days...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29659838/comparative-methylome-analysis-of-icf-patients-identifies-heterochromatin-loci-that-require-zbtb24-cdca7-and-hells-for-their-methylated-state
#14
Guillaume Velasco, Giacomo Grillo, Nizar Touleimat, Laure Ferry, Ivana Ivkovic, Florence Ribierre, Jean-François Deleuze, Sophie Chantalat, Capucine Picard, Claire Francastel
Alterations of DNA methylation landscapes and machinery are a hallmark of many human diseases. A prominent case is the ICF syndrome, a rare autosomal recessive immunological/neurological disorder diagnosed by the loss of DNA methylation at (peri)centromeric repeats and its associated chromosomal instability. It is caused by mutations in the de novo DNA methyltransferase DNMT3B in about half of the patients (ICF1). In the remainder, the striking identification of mutations in factors devoid of DNA methyltransferase activity, ZBTB24 (ICF2), CDCA7 (ICF3) or HELLS (ICF4), raised key questions about common or distinguishing DNA methylation alterations downstream of these mutations and hence, about the functional link between the four factors...
April 12, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29644724/a-novel-missense-mutation-in-grin2a-causes-a-nonepileptic-neurodevelopmental-disorder
#15
Ana Fernández-Marmiesse, Hirofumi Kusumoto, Saray Rekarte, Iria Roca, Jin Zhang, Scott J Myers, Stephen F Traynelis, Mª Luz Couce, Luis Gutierrez-Solana, Hongjie Yuan
BACKGROUND: Mutations in the GRIN2A gene, which encodes the GluN2A (glutamate [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor, have been identified in patients with epilepsy-aphasia spectrum disorders, idiopathic focal epilepsies with centrotemporal spikes, and epileptic encephalopathies with severe developmental delay. However, thus far, mutations in this gene have not been associated with a nonepileptic neurodevelopmental disorder with dystonia. OBJECTIVES: The objective of this study was to identify the disease-causing gene in 2 siblings with neurodevelopmental and movement disorders with no epileptiform abnormalities...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29625060/de-novo-dna-methylation-marking-the-path-from-stem-cell-to-neural-fate
#16
Ayana Sawai, Jeremy S Dasen
DNA methylation is an epigenetic mark that plays pivotal roles in gene regulation, but its functions in neural fate decisions are poorly understood. In this issue of Cell Stem Cell, Ziller et al. (2018) show that the de novo methyltransferase Dnmt3a ensures efficient generation of motor neurons from stem cells.
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29620943/epigenome-wide-analysis-reveals-specific-dna-hypermethylation-of-t-cells-during-human-hematopoietic-differentiation
#17
J Ramón Tejedor, Clara Bueno, Isabel Cobo, Gustavo F Bayón, Cristina Prieto, Cristina Mangas, Raúl F Pérez, Pablo Santamarina, Rocío G Urdinguio, Pablo Menéndez, Mario F Fraga, Agustín F Fernández
AIM: Epigenetic regulation plays an important role in cellular development and differentiation. A detailed map of the DNA methylation dynamics that occur during cell differentiation would contribute to decipher the molecular networks governing cell fate commitment. METHODS: Illumina MethylationEPIC BeadChip platform was used to describe the genome-wide DNA methylation changes observed throughout hematopoietic maturation by analyzing multiple myeloid and lymphoid hematopoietic cell types...
April 5, 2018: Epigenomics
https://www.readbyqxmd.com/read/29567711/early-life-experience-drives-structural-variation-of-neural-genomes-in-mice
#18
Tracy A Bedrosian, Carolina Quayle, Nicole Novaresi, Fred H Gage
The brain is a genomic mosaic owing to somatic mutations that arise throughout development. Mobile genetic elements, including retrotransposons, are one source of somatic mosaicism in the brain. Retrotransposition may represent a form of plasticity in response to experience. Here, we use droplet digital polymerase chain reaction to show that natural variations in maternal care mediate the mobilization of long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons in the hippocampus of the mouse brain...
March 23, 2018: Science
https://www.readbyqxmd.com/read/29551301/dissecting-the-functional-consequences-of-de-novo-dna-methylation-dynamics-in-human-motor-neuron-differentiation-and-physiology
#19
Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y Meltzer, Andreas Gnirke, C J Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing...
March 14, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29487849/prdm14-is-a-unique-epigenetic-regulator-stabilizing-transcriptional-networks-for-pluripotency
#20
REVIEW
Yoshiyuki Seki
PR-domain containing protein 14 (PRDM14) is a site-specific DNA-binding protein and is required for establishment of pluripotency in embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. DNA methylation status is regulated by the balance between de novo methylation and passive/active demethylation, and global DNA hypomethylation is closely associated with cellular pluripotency and totipotency. PRDM14 ensures hypomethylation in mouse ESCs and PGCs through two distinct layers, transcriptional repression of the DNA methyltransferases Dnmt3a/b/l and active demethylation by recruitment of TET proteins...
2018: Frontiers in Cell and Developmental Biology
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