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De novo DNA Methylation

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https://www.readbyqxmd.com/read/28931725/yap-taz-mediated-activation-of-serine-metabolism-and-histone-methylation-is-critical-for-lkb1-deficient-breast-cancer-progression
#1
Qi Wu, Juanjuan Li, Si Sun, Xinyue Chen, Hanpu Zhang, Bei Li, Shengrong Sun
The crucial interplay between metabolic remodeling and the epigenetics could contribute to promote cancer progression. A remarkable association within interaction, LKB1 has been reported, suggesting that the expression of key enzymes involving de novo serine synthesis and DNA methyltransferases like DNMT1 and DNMT3A increase LKB1-deficiency cells. However, the complex interactional link between metabolic remodeling and the epigenetics is still unclear. Hence, we focus on the relationship between YAP/TAZ and serine metabolism to control methylation of DNA or histone in breast cancer with LKB1-deficiency...
September 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28930691/dna-methylome-analysis-identifies-transcription-factor-based-epigenomic-signatures-of-multilineage-competence-in-neural-stem-progenitor-cells
#2
Tsukasa Sanosaka, Takuya Imamura, Nobuhiko Hamazaki, MuhChyi Chai, Katsuhide Igarashi, Maky Ideta-Otsuka, Fumihito Miura, Takashi Ito, Nobuyuki Fujii, Kazuho Ikeo, Kinichi Nakashima
Regulation of the epigenome during in vivo specification of brain stem cells is still poorly understood. Here, we report DNA methylome analyses of directly sampled cortical neural stem and progenitor cells (NS/PCs) at different development stages, as well as those of terminally differentiated cortical neurons, astrocytes, and oligodendrocytes. We found that sequential specification of cortical NS/PCs is regulated by two successive waves of demethylation at early and late development stages, which are responsible for the establishment of neuron- and glia-specific low-methylated regions (LMRs), respectively...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28923089/dna-epigenome-editing-using-crispr-cas-suntag-directed-dnmt3a
#3
Yung-Hsin Huang, Jianzhong Su, Yong Lei, Lorenzo Brunetti, Michael C Gundry, Xiaotian Zhang, Mira Jeong, Wei Li, Margaret A Goodell
BACKGROUND: DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function to regions of DNA methylation is limited by the poor correlation between global patterns of DNA methylation and gene expression. RESULTS: Here, we utilize nuclease-deactivated Cas9 protein fused to repetitive peptide epitopes (SunTag) recruiting multiple copies of antibody-fused de novo DNA methyltransferase 3A (DNMT3A) (dCas9-SunTag-DNMT3A) to amplify the local DNMT3A concentration to methylate genomic sites of interest...
September 18, 2017: Genome Biology
https://www.readbyqxmd.com/read/28903418/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#4
Sayaka Funata, Keisuke Matsusaka, Ryota Yamanaka, Shogo Yamamoto, Atsushi Okabe, Masaki Fukuyo, Hiroyuki Aburatani, Masashi Fukayama, Atsushi Kaneda
Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28872462/haploinsufficiency-for-dna-methyltransferase-3a-predisposes-hematopoietic-cells-to-myeloid-malignancies
#5
Christopher B Cole, David A Russler-Germain, Shamika Ketkar, Angela M Verdoni, Amanda M Smith, Celia V Bangert, Nichole M Helton, Mindy Guo, Jeffery M Klco, Shelly O'Laughlin, Catrina Fronick, Robert Fulton, Gue Su Chang, Allegra A Petti, Christopher A Miller, Timothy J Ley
The gene that encodes de novo DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia genomes. Point mutations at position R882 have been shown to cause a dominant negative loss of DNMT3A methylation activity, but 15% of DNMT3A mutations are predicted to produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with WT DNMT3A, strongly supporting the haploinsufficiency hypothesis...
September 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28858608/correction-in-vivo-targeting-of-de-novo-dna-methylation-by-histone-modifications-in-yeast-and-mouse
#6
Marco Morselli, William A Pastor, Barbara Montanini, Kevin Nee, Roberto Ferrari, Kai Fu, Giancarlo Bonora, Liudmilla Rubbi, Amander T Clark, Simone Ottonello, Steven E Jacobsen, Matteo Pellegrini
No abstract text is available yet for this article.
August 31, 2017: ELife
https://www.readbyqxmd.com/read/28831743/recurrent-establishment-of-de-novo-centromeres-in-the-pericentromeric-region-of-maize-chromosome-3
#7
Hainan Zhao, Zixian Zeng, Dal-Hoe Koo, Bikram S Gill, James A Birchler, Jiming Jiang
Centromeres can arise de novo from non-centromeric regions, which are often called "neocentromeres." Neocentromere formation provides the best evidence for the concept that centromere function is not determined by the underlying DNA sequences, but controlled by poorly understood epigenetic mechanisms. Numerous neocentromeres have been reported in several plant and animal species. However, it has been elusive how and why a specific chromosomal region is chosen to be a new centromere during the neocentromere activation events...
August 22, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28820723/a-lncrna-fine-tunes-the-dynamics-of-a-cell-state-transition-involving-lin28-let-7-and-de-novo-dna-methylation
#8
Meng Amy Li, Paulo P Amaral, Priscilla Cheung, Jan H Bergmann, Masaki Kinoshita, Tüzer Kalkan, Meryem Ralser, Sam Robson, Ferdinand von Meyenn, Maike Paramor, Fengtang Yang, Caifu Chen, Jennifer Nichols, David L Spector, Tony Kouzarides, Lin He, Austin Smith
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28800418/lighting-the-shadows-methods-that-expose-nuclear-and-cytoplasmic-gene-regulatory-control
#9
REVIEW
Travis A Lee, Julia Bailey-Serres
Within cells, myriad interconnected processes orchestrate the progression of gene expression from chromatin, to mRNA, and to protein. Assessment of DNA methylation, histone modification, transcript isoform abundance, and the proteome are frequently performed to examine this progression, but do not resolve many intermediary steps in the coordinated regulation of gene expression. Here, we consider single and multiplexed technologies that yield genome-wide assessment of gene and mRNA activity, from transcription factor access to DNA to de novo synthesis of protein...
August 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28792951/how-stable-is-repression-of-disallowed-genes-in-pancreatic-islets-in-response-to-metabolic-stress
#10
Katleen Lemaire, Mikaela Granvik, Anica Schraenen, Lotte Goyvaerts, Leentje Van Lommel, Ana Gómez-Ruiz, Peter In 't Veld, Patrick Gilon, Frans Schuit
The specific phenotype of mature differentiated beta cells not only depends on the specific presence of genes that allow beta cell function but also on the selective absence of housekeeping genes ("disallowed genes") that would interfere with this function. Recent studies have shown that both histone modifications and DNA methylation via the de novo methyltransferase DNMT3A are involved in repression of disallowed genes in neonatal beta cells when these cells acquire their mature phenotype. It is unknown, however, if the environmental influence of advanced age, pregnancy and the metabolic stress of high fat diet or diabetes could alter the repression of disallowed genes in beta cells...
2017: PloS One
https://www.readbyqxmd.com/read/28783101/analysis-of-argonaute-4-associated-long-non-coding-rna-in-arabidopsis-thaliana-sheds-novel-insights-into-gene-regulation-through-rna-directed-dna-methylation
#11
Phil Chi Khang Au, Elizabeth S Dennis, Ming-Bo Wang
RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains poorly understood and few RdDM target genes have been identified. In this study, we obtained sequences of RdDM-associated lncRNAs using nuclear RNA immunoprecipitation against ARGONAUTE 4 (AGO4), a key component of RdDM that binds specifically with the lncRNA...
August 7, 2017: Genes
https://www.readbyqxmd.com/read/28753554/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#12
Sayaka Funata, Keisuke Matsusaka, Ryota Yamanaka, Shogo Yamamoto, Atsushi Okabe, Masaki Fukuyo, Hiroyuki Aburatani, Masashi Fukayama, Atsushi Kaneda
Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751638/targeted-dna-methylation-in-human-cells-using-engineered-dcas9-methyltransferases
#13
Tina Xiong, Glenna E Meister, Rachael E Workman, Nathaniel C Kato, Michael J Spellberg, Fulya Turker, Winston Timp, Marc Ostermeier, Carl D Novina
Mammalian genomes exhibit complex patterns of gene expression regulated, in part, by DNA methylation. The advent of engineered DNA methyltransferases (MTases) to target DNA methylation to specific sites in the genome will accelerate many areas of biological research. However, targeted MTases require clear design rules to direct site-specific DNA methylation and minimize the unintended effects of off-target DNA methylation. Here we report a targeted MTase composed of an artificially split CpG MTase (sMTase) with one fragment fused to a catalytically-inactive Cas9 (dCas9) that directs the functional assembly of sMTase fragments at the targeted CpG site...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28749988/switching-of-dominant-retrotransposon-silencing-strategies-from-posttranscriptional-to-transcriptional-mechanisms-during-male-germ-cell-development-in-mice
#14
Kota Inoue, Kenji Ichiyanagi, Kei Fukuda, Michael Glinka, Hiroyuki Sasaki
Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs) combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+) RNAs (transcriptome) in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28746368/the-genome-wide-identification-and-transcriptional-levels-of-dna-methyltransferases-and-demethylases-in-globe-artichoke
#15
Silvia Gianoglio, Andrea Moglia, Alberto Acquadro, Cinzia Comino, Ezio Portis
Changes to the cytosine methylation status of DNA, driven by the activity of C5 methyltransferases (C5-MTases) and demethylases, exert an important influence over development, transposon movement, gene expression and imprinting. Three groups of C5-MTase enzymes have been identified in plants, namely MET (methyltransferase 1), CMT (chromomethyltransferases) and DRM (domains rearranged methyltransferases). Here the repertoire of genes encoding C5-MTase and demethylase by the globe artichoke (Cynara cardunculus var...
2017: PloS One
https://www.readbyqxmd.com/read/28746308/derivation-of-ground-state-female-es-cells-maintaining-gamete-derived-dna-methylation
#16
Masaki Yagi, Satoshi Kishigami, Akito Tanaka, Katsunori Semi, Eiji Mizutani, Sayaka Wakayama, Teruhiko Wakayama, Takuya Yamamoto, Yasuhiro Yamada
Inhibitors of Mek1/2 and Gsk3β, known as 2i, enhance the derivation of embryonic stem (ES) cells and promote ground-state pluripotency in rodents. Here we show that the derivation of female mouse ES cells in the presence of 2i and leukaemia inhibitory factor (2i/L ES cells) results in a widespread loss of DNA methylation, including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, early-passage 2i/L ES cells efficiently differentiate into somatic cells, and this process requires genome-wide de novo DNA methylation...
August 10, 2017: Nature
https://www.readbyqxmd.com/read/28740121/overexpression-of-dnmt3b-target-genes-during-enteric-nervous-system-development-contribute-to-the-onset-of-hirschsprung-disease
#17
Leticia Villalba-Benito, Ana Torroglosa, Raquel María Fernández, Macarena Ruíz-Ferrer, María José Moya-Jiménez, Guillermo Antiñolo, Salud Borrego
Hirschsprung disease (HSCR) is attributed to a failure of neural crest cells (NCCs) to migrate, proliferate, differentiate and/or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. ENS formation is the result from a specific gene expression pattern regulated by epigenetic events, such DNA methylation by the DNA methyltransferases (DNMTs), among other mechanisms. Specifically, DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation and in HSCR...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28648661/de-novo-epigenetic-programs-inhibit-pd-1-blockade-mediated-t-cell-rejuvenation
#18
Hazem E Ghoneim, Yiping Fan, Ardiana Moustaki, Hossam A Abdelsamed, Pradyot Dash, Pranay Dogra, Robert Carter, Walid Awad, Geoff Neale, Paul G Thomas, Ben Youngblood
Immune-checkpoint-blockade (ICB)-mediated rejuvenation of exhausted T cells has emerged as a promising approach for treating various cancers and chronic infections. However, T cells that become fully exhausted during prolonged antigen exposure remain refractory to ICB-mediated rejuvenation. We report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. Whole-genome bisulfite sequencing of antigen-specific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progressively acquired heritable de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade treatment...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28630288/intact-pirna-pathway-prevents-l1-mobilization-in-male-meiosis
#19
Simon J Newkirk, Suman Lee, Fiorella C Grandi, Valeriya Gaysinskaya, James M Rosser, Nicole Vanden Berg, Cathryn A Hogarth, Maria C N Marchetto, Alysson R Muotri, Michael D Griswold, Ping Ye, Alex Bortvin, Fred H Gage, Jef D Boeke, Wenfeng An
The PIWI-interacting RNA (piRNA) pathway is essential for retrotransposon silencing. In piRNA-deficient mice, L1-overexpressing male germ cells exhibit excessive DNA damage and meiotic defects. It remains unknown whether L1 expression simply highlights piRNA deficiency or actually drives the germ-cell demise. Specifically, the sheer abundance of genomic L1 copies prevents reliable quantification of new insertions. Here, we developed a codon-optimized L1 transgene that is controlled by an endogenous mouse L1 promoter...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28624556/a-64-bp-sequence-containing-the-gaaga-motif-is-essential-for-camv-35s-promoter-methylation-in-gentian
#20
Asahi Shimada, Azusa Okumura, Satoshi Yamasaki, Yuji Iwata, Nozomu Koizumi, Masahiro Nishihara, Kei-Ichiro Mishiba
This study investigated sequence specificity and perenniality of DNA methylation in the cauliflower mosaic virus (CaMV) 35S promoter of transgenic gentian (Gentiana triflora×G. scabra) plants. Unlike conventional transgene silencing models, 35S promoter hypermethylation in gentian is species-specific and occurs irrespective of the T-DNA copy number and genomic location. Modified 35S promoters were introduced into gentian, and single-copy transgenic lines were selected for methylation analysis. Modified 35S promoter lacking a core (-90) region [35S(Δcore)] in gentian conferred hypermethylation and high levels of de novo methylation of the CpHpH/CpCpG sites in the 35S enhancer regions (-298 to -241 and -148 to -85)...
June 15, 2017: Biochimica et Biophysica Acta
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