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De novo DNA Methylation

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https://www.readbyqxmd.com/read/27901321/copy-number-variants-in-a-population-based-investigation-of-klippel-trenaunay-syndrome
#1
Aggeliki Dimopoulos, Robert J Sicko, Denise M Kay, Shannon L Rigler, Ruzong Fan, Paul A Romitti, Marilyn L Browne, Charlotte M Druschel, Michele Caggana, Lawrence C Brody, James L Mills
Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder that is thought to occur sporadically; however, reports of familial occurrence suggest a genetic component. We examined KTS cases to identify novel, potentially causal copy number variants (CNVs). We identified 17 KTS cases from all live-births occurring in New York (1998-2010). Extracted DNA was genotyped using Illumina microarrays and CNVs were called using PennCNV software. CNVs selected for follow-up had ≥10 single nucleotide polymorphisms (SNPs) and minimal overlap with in-house controls or controls from the Database of Genomic Variants...
November 30, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27899265/discovery-of-novel-dna-methyltransferase-3a-inhibitors-via-structure-based-virtual-screening-and-biological-assays
#2
Zhiyuan Shao, Pan Xu, Wen Xu, Linjuan Li, Shien Liu, Rukang Zhang, Yu-Chih Liu, Chenhua Zhang, Shijie Chen, Cheng Luo
DNA methyltransferases are involved in diverse biological processes and abnormal methylation patterns play essential roles in cancer initiation and progression. DNA methyltransferase 3A (DNMT3A) acting as a de novo DNA methyltransferase, has gained widespread attention especially in haematological diseases. To date, large numbers of DNMTs inhibitors have been discovered, however, the small molecular inhibitors targeting DNMT3A are still in its infancy. In this study, structure-based virtual screening in combination with biological assays was performed to discovery potent novel DNMT3A inhibitors...
November 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27895716/widespread-recovery-of-methylation-at-gametic-imprints-in-hypomethylated-mouse-stem-cells-following-rescue-with-dnmt3a2
#3
Avinash Thakur, Sarah-Jayne Mackin, Rachelle E Irwin, Karla M O'Neill, Gareth Pollin, Colum Walsh
BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27886677/differences-in-global-dna-methylation-of-testicular-seminoma-are-not-associated-with-changes-in-histone-modifications-clinical-prognosis-braf-mutations-or-gene-expression
#4
Louise Holm Pedersen, John E Nielsen, Gedske Daugaard, Thomas V O Hansen, Ewa Rajpert-De Meyts, Kristian Almstrup
Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively...
November 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27884978/estrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#5
Vijaya Narasihma Reddy Gajulapalli, Vijaya Lakshmi Malisetty, Suresh Kumar Chitta, Bramanandam Manavathi
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of ERα expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate estrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable, to answer that two important approaches are considered: 1) Understanding the cellular origin of heterogeneity and ER negativity in breast cancers, and 2) characterization of molecular regulators of endocrine resistance...
November 24, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27880916/nrl-regulated-transcriptome-dynamics-of-developing-rod-photoreceptors
#6
Jung-Woong Kim, Hyun-Jin Yang, Matthew John Brooks, Lina Zelinger, Gökhan Karakülah, Norimoto Gotoh, Alexis Boleda, Linn Gieser, Felipe Giuste, Dustin Thad Whitaker, Ashley Walton, Rafael Villasmil, Jennifer Joanna Barb, Peter Jonathan Munson, Koray Dogan Kaya, Vijender Chaitankar, Tiziana Cogliati, Anand Swaroop
Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27856912/the-dna-methyltransferase-dnmt3c-protects-male-germ-cells-from-transposon-activity
#7
Joan Barau, Aurélie Teissandier, Natasha Zamudio, Stéphanie Roy, Valérie Nalesso, Yann Hérault, Florian Guillou, Déborah Bourc'his
DNA methylation is prevalent in mammalian genomes and plays a central role in the epigenetic control of development. The mammalian DNA methylation machinery is thought to be composed of three DNA methyltransferase enzymes (DNMT1, DNMT3A, and DNMT3B) and one cofactor (DNMT3L). Here, we describe the discovery of Dnmt3C, a de novo DNA methyltransferase gene that evolved via a duplication of Dnmt3B in rodent genomes and was previously annotated as a pseudogene. We show that DNMT3C is the enzyme responsible for methylating the promoters of evolutionarily young retrotransposons in the male germ line and that this specialized activity is required for mouse fertility...
November 18, 2016: Science
https://www.readbyqxmd.com/read/27854126/human-adipogenesis-is-associated-with-genome-wide-dna-methylation-and-gene-expression-changes
#8
Christa Broholm, Anders Henrik Olsson, Alexander Perfilyev, Linn Gillberg, Ninna Schiøler Hansen, Ashfaq Ali, Brynjulf Mortensen, Charlotte Ling, Allan Vaag
AIM: To define the genomic distribution and function of DNA methylation changes during human adipogenesis. METHODS: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes. RESULTS: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830 transcripts after differentiation. De novo methylation was observed across all genomic elements...
November 17, 2016: Epigenomics
https://www.readbyqxmd.com/read/27846393/decoding-the-dna-methylome-of-mantle-cell-lymphoma-in-the-light-of-the-entire-b-cell-lineage
#9
Ana C Queirós, Renée Beekman, Roser Vilarrasa-Blasi, Martí Duran-Ferrer, Guillem Clot, Angelika Merkel, Emanuele Raineri, Nuria Russiñol, Giancarlo Castellano, Sílvia Beà, Alba Navarro, Marta Kulis, Núria Verdaguer-Dot, Pedro Jares, Anna Enjuanes, María José Calasanz, Anke Bergmann, Inga Vater, Itziar Salaverría, Harmen J G van de Werken, Wyndham H Wilson, Avik Datta, Paul Flicek, Romina Royo, Joost Martens, Eva Giné, Armando Lopez-Guillermo, Hendrik G Stunnenberg, Wolfram Klapper, Christiane Pott, Simon Heath, Ivo G Gut, Reiner Siebert, Elías Campo, José I Martín-Subero
We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27843576/micrornas-interfere-with-dna-methylation-in-rheumatoid-arthritis-synovial-fibroblasts
#10
Niharika Gaur, Emmanuel Karouzakis, Selene Glück, Edvardas Bagdonas, Astrid Jüngel, Beat A Michel, Renate E Gay, Steffen Gay, Mojca Frank-Bertoncelj, Michel Neidhart
BACKGROUND: The DNA of rheumatoid arthritis synovial fibroblasts (RASF) is globally hypomethylated; this contributes to an aggressive behaviour. In an attempt to remethylate these cells, we supplemented with methyl donors. We investigated the possible interference of microRNAs (miRs). MATERIAL AND METHODS: RASF were treated with L-methionine or betaine. Transcripts of de novo methyltransferases (DNMTs) and miRs were measured by real-time PCR, and a transcription PCR array was performed...
2016: RMD Open
https://www.readbyqxmd.com/read/27833659/identification-of-activated-enhancers-and-linked-transcription-factors-in-breast-prostate-and-kidney-tumors-by-tracing-enhancer-networks-using-epigenetic-traits
#11
Suhn Kyong Rhie, Yu Guo, Yu Gyoung Tak, Lijing Yao, Hui Shen, Gerhard A Coetzee, Peter W Laird, Peggy J Farnham
BACKGROUND: Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27829228/tet2-functions-as-a-resistance-factor-against-dna-methylation-acquisition-during-epstein-barr-virus-infection
#12
Hiroe Namba-Fukuyo, Sayaka Funata, Keisuke Matsusaka, Masaki Fukuyo, Bahityar Rahmutulla, Yasunobu Mano, Masashi Fukayama, Hiroyuki Aburatani, Atsushi Kaneda
Extensive DNA methylation is observed in gastric cancer with Epstein-Barr virus (EBV) infection, and EBV infection is the cause to induce this extensive hypermethylaton phenotype in gastric epithelial cells. However, some 5' regions of genes do not undergo de novo methylation, despite the induction of methylation in surrounding regions, suggesting the existence of a resistance factor against DNA methylation acquisition. We conducted an RNA-seq analysis of gastric epithelial cells with and without EBV infection and found that TET family genes, especially TET2, were repressed by EBV infection at both mRNA and protein levels...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826839/structure-and-mechanism-of-plant-dna-methyltransferases
#13
Jiamu Du
DNA methylation is an important epigenetic mark that functions in eukaryotes from fungi to animals and plants, where it plays a crucial role in the regulation of epigenetic silencing. Once the methylation mark is established by the de novo DNA methyltransferase (MTase), it requires specific regulatory mechanisms to maintain the methylation state during chromatin replication, both during meiosis and mitosis. Plants have distinct DNA methylation patterns that are both established and maintained by unique DNA MTases and are regulated by plant-specific pathways...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826835/domain-structure-of-the-dnmt1-dnmt3a-and-dnmt3b-dna-methyltransferases
#14
Shoji Tajima, Isao Suetake, Kohei Takeshita, Atsushi Nakagawa, Hironobu Kimura
In mammals, three DNA methyltransferases, Dnmt1, Dnmt3a, and Dnmt3b, have been identified. Dnmt3a and Dnmt3b are responsible for establishing DNA methylation patterns produced through their de novo-type DNA methylation activity in implantation stage embryos and during germ cell differentiation. Dnmt3-like (Dnmt3l), which is a member of the Dnmt3 family but does not possess DNA methylation activity, was reported to be indispensable for global methylation in germ cells. Once the DNA methylation patterns are established, maintenance-type DNA methyltransferase Dnmt1 faithfully propagates them to the next generation via replication...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27824296/lens-development-requires-dnmt1-but-takes-place-normally-in-the-absence-of-both-dnmt3a-and-dnmt3b-activity
#15
Thanh V Hoang, Evan R Horowitz, Blake R Chaffee, Peipei Qi, Rachel E Flake, Devin G Bruney, Blake J Rasor, Savana E Rosalez, Brad D Wagner, Michael L Robinson
Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected...
November 8, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27813706/global-genome-repair-factors-control-dna-methylation-patterns-in-arabidopsis
#16
Catherine Schalk, Jean Molinier
As obligate photosynthetic organisms plants are particularly exposed to the damaging effects of excess light and ultraviolet wavelengths, which can impact genome and epigenome dynamics by inducing DNA sequence and chromatin alterations. DNA DAMAGE-BINDING PROTEIN 2 (DDB2) is the main factor involved in the recognition of UV-induced DNA lesions during Global Genome Repair (GGR) in mammals and in plants. (1) In a recent study we reported that, in Arabidopsis, loss of DDB2 function alters DNA methylation patterns at many repeat loci and protein coding genes...
November 4, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/27803193/imprints-and-dppa3-are-bypassed-during-pluripotency-and-differentiation-coupled-methylation-reprogramming-in-testicular-germ-cell-tumors
#17
J Keith Killian, Lambert C J Dorssers, Britton Trabert, Ad J M Gillis, Michael B Cook, Yonghong Wang, Joshua J Waterfall, Holly Stevenson, William I Smith, Natalia Noyes, Parvathy Retnakumar, J Hans Stoop, J Wolter Oosterhuis, Paul S Meltzer, Katherine A McGlynn, Leendert H J Looijenga
Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and differentiated somatic references...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27799474/mirdnmr-a-gene-centered-database-of-background-de-novo-mutation-rates-in-human
#18
Yi Jiang, Zhongshan Li, Zhenwei Liu, Denghui Chen, Wanying Wu, Yaoqiang Du, Liying Ji, Zi-Bing Jin, Wei Li, Jinyu Wu
De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required...
October 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27786608/de-novo-methylation-in-male-germ-cells-of-the-common-marmoset-monkey-occurs-during-postnatal-development-and-is-maintained-in-vitro
#19
Daniel Langenstroth-Röwer, Jörg Gromoll, Joachim Wistuba, Ina Tröndle, Sandra Laurentino, Stefan Schlatt, Nina Neuhaus
The timing of de novo DNA methylation in male germ cells during human testicular development is yet unsolved. Apart from that, the stability of established imprinting patterns in vitro is controversially discussed. This study aimed at determining the timing of DNA de novo methylation and at assessing the stability of the methylation status in vitro. We employed the marmoset monkey (Callithrix jacchus) as it is considered the best non-human primate model for human testicular development. We selected neonatal, pre-pubertal, pubertal, and adult animals (n = 3, each) and assessed germ cell global DNA methylation levels by 5-methyl cytosine staining, and Alu elements and gene-specific methylation (H19, LIT1, SNRPN, MEST, OCT4, MAGE-A4, and DDX-4) by pyrosequencing...
October 27, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27779916/developmental-and-thyroid-hormone-regulation-of-the-dna-methyltransferase-3a-gene-in-xenopus-tadpoles
#20
Yasuhiro Kyono, Laurent M Sachs, Patrice Bilesimo, Luan Wen, Robert J Denver
Thyroid hormone (TH) is essential for normal development in vertebrates. In amphibians, TH controls metamorphosis by inducing tissue-specific gene regulation programs. A hallmark of TH action is the modification of chromatin structure, which underlies changes in gene transcription. We found that mRNA for the de novo DNA methyltransferase (DNMT) dnmt3a, but not dnmt1, increased in the brain of Xenopus tadpoles during metamorphosis in parallel with plasma [TH]. Addition of 3,5,3`-triiodothyronine (T3) to the rearing water caused a time-dependent increase in dnmt3a mRNA in tadpole brain, tail and hind limb...
October 25, 2016: Endocrinology
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