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De novo DNA Methylation

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https://www.readbyqxmd.com/read/28286768/epigenetic-guardian-a-review-of-the-dna-methyltransferase-dnmt3a-in-acute-myeloid-leukaemia-and-clonal-haematopoiesis
#1
REVIEW
Sabah F Chaudry, Timothy J T Chevassut
Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28267064/nerve-injury-induced-epigenetic-silencing-of-opioid-receptors-controlled-by-dnmt3a-in-primary-afferent-neurons
#2
Linlin Sun, Jian-Yuan Zhao, Xiyao Gu, Lingli Liang, Shaogen Wu, Kai Mo, Jian Feng, Weixiang Guo, Jun Zhang, Alex Bekker, Xinyu Zhao, Eric J Nestler, Yuan-Xiang Tao
Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase-(DNMT-) triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu opioid receptor (MOR) and kappa opioid receptor (KOR) proteins in the injured DRG...
March 4, 2017: Pain
https://www.readbyqxmd.com/read/28256047/maternal-mutations-of-foxf1-cause-alveolar-capillary-dysplasia-despite-not-being-imprinted
#3
Miguel Alsina Casanova, Ana Monteagudo-Sánchez, Luciana Rodriguez Guerineau, Franck Court, Isabel Gazquez Serrano, Loreto Martorell, Carlota Rovira Zurriaga, Gudrun E Moore, Miho Ishida, Montserrat Castañon, Elisenda Moliner Calderon, David Monk, Julio Moreno Hernando
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare cause of pulmonary hypertension in newborns. Maternally inherited point mutations in Forkhead Box F1 gene (FOXF1), deletions of the gene or its long-range enhancers on the maternal allele are responsible for this neonatal lethal disorder. Here we describe monozygotic twins and one full-term newborn with ACD and gastrointestinal malformations caused by de novo mutations of FOXF1 on the maternal inherited alleles. Since this parental transmission is consistent with genomic imprinting, the parent-of-origin specific monoallelic expression of genes, we have undertaken a detailed analysis of both allelic expression and DNA methylation...
March 3, 2017: Human Mutation
https://www.readbyqxmd.com/read/28238081/dna-methyltransferases-contribute-to-the-fungal-development-stress-tolerance-and-virulence-of-the-entomopathogenic-fungus-metarhizium-robertsii
#4
Yulong Wang, Tiantian Wang, Lintao Qiao, Jianyu Zhu, Jinrui Fan, Tingting Zhang, Zhang-Xun Wang, Wanzhen Li, Anhui Chen, Bo Huang
DNA methylation is an important epigenetic mark in mammals, plants, and fungi and depends on multiple genetic pathways involving de novo and maintenance DNA methyltransferases (DNMTases). Metarhizium robertsii, a model system for investigating insect-fungus interactions, has been used as an environmentally friendly alternative to chemical insecticides. However, little is known concerning the molecular basis for DNA methylation. Here, we report on the roles of two DNMTases (MrRID and MrDIM-2) by characterizing ΔMrRID, ΔMrDIM-2, and ΔRID/ΔDIM-2 mutants...
February 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28225069/testicular-dnmt3-expression-and-global-dna-methylation-are-down-regulated-by-gonadotropin-releasing-hormones-in-the-ricefield-eel-monopterus-albus
#5
Yize Zhang, Xin Sun, Lihong Zhang, Weimin Zhang
In vertebrates, DNA methyltransferase 3 (Dnmt3) homologues are responsible for de novo DNA methylation and play important roles in germ cell development. In the present study, four dnmt3 genes, dnmt3aa, dnmt3ab, dnmt3ba and dnmt3bb.1, were identified in ricefield eels. Real-time quantitative PCR analysis showed that all four dnmt3 mRNAs were detected broadly in tissues examined, with testicular expression at relatively high levels. In the testis, immunostaining for all four Dnmt3 forms was mainly localized to spermatocytes, which also contained highly methylated DNA...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223440/idn2-interacts-with-rpa-and-facilitates-dna-double-strand-break-repair-by-homologous-recombination-in-arabidopsis
#6
Mingming Liu, Zhaoqing Ba, Pedro Costa-Nunes, Wei Wei, Lanxia Li, Fansi Kong, Yan Li, Jijie Chai, Olga Pontes, Yijun Qi
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination (HR)-mediated DSB repair in Arabidopsis thaliana. Here we show that INVOLVED IN DE NOVO 2 (IDN2), a double-stranded RNA (dsRNA) binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28207953/sgs1-a-neomorphic-nac52-allele-impairing-ptgs-through-sgs3-down-regulation
#7
Nicolas Butel, Ivan Le Masson, Nathalie Bouteiller, Hervé Vaucheret, Taline Elmayan
Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) origins. Genetic screens based on the reactivation of silenced transgenes have long been used to identify cellular PTGS components and regulators. Here we show that the first isolated PTGS-deficient mutant, sgs1, is impaired in the transcription factor NAC52. This mutant exhibits striking similarities with a mutant impaired in the H3K4me3 demethylase JMJ14 isolated from the same genetic screen...
February 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28198363/gut-memories-do-not-fade-epigenetic-regulation-of-lasting-gut-homing-receptor-expression-in-cd4-memory-t-cells
#8
B A Szilagyi, J Triebus, C Kressler, M de Almeida, S Tierling, P Durek, M Mardahl, A Szilagyi, S Floess, J Huehn, U Syrbe, J Walter, J K Polansky, A Hamann
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28193737/exogenous-transposable-elements-circumvent-identity-based-silencing-permitting-the-dissection-of-expression-dependent-silencing
#9
Dalen Fultz, R Keith Slotkin
The propagation of epigenetic marks has received a great deal of attention, yet the initiation of epigenetic silencing of a new transgene, virus, or transposable element (TE) remains enigmatic. The overlapping and simultaneous function of multiple silencing mechanisms has obscured this area of investigation. Here, we revealed two broad mechanisms that can initiate silencing independently: identity-based and expression-dependent silencing. We found that identity-based silencing is targeted by 21- to 22-nucleotide or 24-nucleotide small interfering RNAs (siRNAs) generated from previously silenced regions of the genome...
February 2017: Plant Cell
https://www.readbyqxmd.com/read/28182669/a-de-novo-loss-of-function-grin2a-mutation-associated-with-childhood-focal-epilepsy-and-acquired-epileptic-aphasia
#10
Kai Gao, Anel Tankovic, Yujia Zhang, Hirofumi Kusumoto, Jin Zhang, Wenjuan Chen, Wenshu XiangWei, Gil H Shaulsky, Chun Hu, Stephen F Traynelis, Hongjie Yuan, Yuwu Jiang
OBJECTIVE: N-methyl-D-aspartate receptors (NMDAR) subunit GRIN2A/GluN2A mutations have been identified in patients with various neurological diseases, such as epilepsy and intellectual disability / developmental delay (ID/DD). In this study, we investigated the phenotype and underlying molecular mechanism of a GRIN2A missense mutation identified by next generation sequencing on idiopathic focal epilepsy using in vitro electrophysiology. METHODS: Genomic DNA of patients with epilepsy and ID/DD were sequenced by targeted next-generation sequencing within 300 genes related to epilepsy and ID/DD...
2017: PloS One
https://www.readbyqxmd.com/read/28153750/rdm16-and-sta1-regulate-differential-usage-of-exon-intron-in-rna-directed-dna-methylation-pathway
#11
Ravi Datta Sharma, Bert Bogaerts, Neha Goyal
The splicing factors RDM16 and STA1 have been reported to play a role in the RNA directed DNA Methylation (RdDM) pathway. In this pathway, small interfering RNAs guide de-novo methylation of homologous DNA sequences. DNA methylation is epigenetic marks, which can suppress transposable elements, repeat sequences and genes. It also affects the chromatin structure. Upon deletion of RDM16 and STA1, previous studies based on gene level analysis were unable to find differentially spliced events implicated in RdDM pathway...
April 20, 2017: Gene
https://www.readbyqxmd.com/read/28123849/dnmt3b-modulates-the-expression-of-cancer-related-genes-and-downregulates-the-expression-of-the-gene-vav3-via-methylation
#12
Irlanda Peralta-Arrieta, Daniel Hernández-Sotelo, Yaneth Castro-Coronel, Marco Antonio Leyva-Vázquez, Berenice Illades-Aguiar
Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo. The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28110250/detection-and-discrimination-of-maintenance-and-de-novo-cpg-methylation-events-using-methylbreak
#13
William Hsu, Augustus T Mercado, George Hsiao, Jui-Ming Yeh, Chung-Yung Chen
Understanding the principles governing the establishment and maintenance activities of DNA methyltransferases (DNMTs) can help in the development of predictive biomarkers associated with genetic disorders and diseases. A detection system was developed that distinguishes and quantifies methylation events using methylation-sensitive endonucleases and molecular beacon technology. MethylBreak (MB) is a 22-mer oligonucleotide with one hemimethylated and two unmethylated CpG sites, which are also recognition sites for Sau96I and SacII, and is attached to a fluorophore and a quencher...
May 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28105934/charm-discovery-of-combinatorial-chromatin-modification-patterns-in-hepatitis-b-virus-x-transformed-mouse-liver-cancer-using-association-rule-mining
#14
Sung Hee Park, Sun-Min Lee, Young-Joon Kim, Sangsoo Kim
BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28065650/network-dynamics-mediate-circadian-clock-plasticity
#15
Abdelhalim Azzi, Jennifer A Evans, Tanya Leise, Jihwan Myung, Toru Takumi, Alec J Davidson, Steven A Brown
A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28064006/versatile-rna-tetra-u-helix-linking-motif-as-a-toolkit-for-nucleic-acid-nanotechnology
#16
My N Bui, M Brittany Johnson, Mathias Viard, Emily Satterwhite, Angelica N Martins, Zhihai Li, Ian Marriott, Kirill A Afonin, Emil F Khisamutdinov
RNA nanotechnology employs synthetically modified ribonucleic acid (RNA) to engineer highly stable nanostructures in one, two, and three dimensions for medical applications. Despite the tremendous advantages in RNA nanotechnology, unmodified RNA itself is fragile and prone to enzymatic degradation. In contrast to use traditionally modified RNA strands e.g. 2'-fluorine, 2'-amine, 2'-methyl, we studied the effect of RNA/DNA hybrid approach utilizing a computer-assisted RNA tetra-uracil (tetra-U) motif as a toolkit to address questions related to assembly efficiency, versatility, stability, and the production costs of hybrid RNA/DNA nanoparticles...
January 4, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#17
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28003281/dnmt3a-in-leukemia
#18
REVIEW
Lorenzo Brunetti, Michael C Gundry, Margaret A Goodell
DNA methylation is an epigenetic process involved in development, aging, and cancer. Although the advent of new molecular techniques has enhanced our knowledge of how DNA methylation alters chromatin and subsequently affects gene expression, a direct link between epigenetic marks and tumorigenesis has not been established. DNMT3A is a de novo DNA methyltransferase that has recently gained relevance because of its frequent mutation in a large variety of immature and mature hematologic neoplasms. DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia (AML) patients making this gene an attractive target for new therapies...
February 1, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28003272/cancer-specific-changes-in-dna-methylation-reveal-aberrant-silencing-and-activation-of-enhancers-in-leukemia
#19
Ying Qu, Lee Siggens, Lina Cordeddu, Verena I Gaidzik, Kasper Karlsson, Lars Bullinger, Konstanze Döhner, Karl Ekwall, Sören Lehmann, Andreas Lennartsson
Acute myeloid leukemia (AML) is characterized by an impaired differentiation process leading to an accumulation of immature blasts in the blood. One feature of cytogenetically normal AML is alterations to the DNA methylome. We analyzed 57 AML patients with normal karyotype by using Illumina's 450k array and showed that aberrant DNA methylation is significantly altered at enhancer regions and that the methylation levels at specific enhancers predict overall survival of AML patients. The majority of sites that become differentially methylated in AML occur in regulatory elements of the human genome...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/27991732/acute-myeloid-leukemia-associated-dnmt3a-p-arg882his-mutation-in-a-patient-with-tatton-brown-rahman-overgrowth-syndrome-as-a-constitutional-mutation
#20
Rika Kosaki, Hiroshi Terashima, Masaya Kubota, Kenjiro Kosaki
DNA methylation plays a critical role in both embryonic development and tumorigenesis and is mediated through various DNA methyltransferases. Constitutional mutations in the de novo DNA methyltransferase DNMT3A cause a recently identified Tatton-Brown-Rahman overgrowth syndrome (TBRS). Somatically acquired mutations in DNMT3A are causally associated with acute myeloid leukemia (AML), and p.Arg882His represents the most prevalent hotspot. So far, no patients with TBRS have been reported to have subsequently developed AML...
January 2017: American Journal of Medical Genetics. Part A
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