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De novo DNA Methylation

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https://www.readbyqxmd.com/read/29346625/complete-genomic-and-transcriptional-landscape-analysis-using-third-generation-sequencing-a-case-study-of-saccharomyces-cerevisiae-cen-pk113-7d
#1
Piroon Jenjaroenpun, Thidathip Wongsurawat, Rui Pereira, Preecha Patumcharoenpol, David W Ussery, Jens Nielsen, Intawat Nookaew
Completion of eukaryal genomes can be difficult task with the highly repetitive sequences along the chromosomes and short read lengths of second-generation sequencing. Saccharomyces cerevisiae strain CEN.PK113-7D, widely used as a model organism and a cell factory, was selected for this study to demonstrate the superior capability of very long sequence reads for de novo genome assembly. We generated long reads using two common third-generation sequencing technologies (Oxford Nanopore Technology (ONT) and Pacific Biosciences (PacBio)) and used short reads obtained using Illumina sequencing for error correction...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29339403/a-phase-1-study-of-azacitidine-combined-with-chemotherapy-in-childhood-leukemia-a-report-from-tacl-consortium
#2
Weili Sun, Timothy Triche, Jemily Malvar, Paul Gaynon, Richard Sposto, Xiaojing Yang, Henrique Bittencourt, Andrew E Place, Yoav Messinger, Chris Fraser, Luciano Dalla-Pozza, Bodour Salhia, Peter Jones, Alan S Wayne, Lia Gore, Todd M Cooper, Gangning Liang
Growing evidence indicates that aberrant DNA hypermethylation is associated with leukemogenesis, chemotherapy resistance, and relapse. DNA methyltransferase inhibitors such as azacitidine and decitabine have been shown to reverse drug resistance and prime leukemia cells to cytotoxic agents in vitro. Here we report the first pediatric phase 1 study using azacitidine in sequence with chemotherapy in patients with relapsed/refractory leukemia. Fourteen patients were enrolled, twelve with acute myeloid leukemia (AML) and two with acute lymphoblastic leukemia (ALL)...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29334780/rules-governing-the-mechanism-of-epigenetic-reprogramming-memory
#3
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
https://www.readbyqxmd.com/read/29327614/intracellular-african-swine-fever-virus-dna-remains-unmethylated-in-infected-vero-cells
#4
Stefanie Weber, Astghik Hakobyan, Hovakim Zakaryan, Walter Doerfler
AIM: Sequence-specific CpG methylation of eukaryotic promoters is an important epigenetic signal for long-term gene silencing. We have now studied the methylation status of African swine fever virus (ASFV) DNA at various times after infection of Vero cells in culture. METHODS & RESULTS: ASFV DNA was detectable throughout the infection cycle and was found unmethylated in productively infected Vero cells as documented by bisulfite sequencing of 13 viral DNA segments...
January 12, 2018: Epigenomics
https://www.readbyqxmd.com/read/29324392/abnormal-rna-splicing-and-genomic-instability-after-induction-of-dnmt3a-mutations-by-crispr-cas9-gene-editing
#5
Lauren G Banaszak, Valentina Giudice, Xin Zhao, Zhijie Wu, Shouguo Gao, Kohei Hosokawa, Keyvan Keyvanfar, Danielle M Townsley, Fernanda Gutierrez-Rodrigues, Maria Del Pilar Fernandez Ibanez, Sachiko Kajigaya, Neal S Young
DNA methyltransferase 3A (DNMT3A) mediates de novo DNA methylation. Mutations in DNMT3A are associated with hematological malignancies, most frequently acute myeloid leukemia. DNMT3A mutations are hypothesized to establish a pre-leukemic state, rendering cells vulnerable to secondary oncogenic mutations and malignant transformation. However, the mechanisms by which DNMT3A mutations contribute to leukemogenesis are not well-defined. Here, we successfully created four DNMT3A-mutated K562 cell lines with frameshift mutations resulting in truncated DNMT3A proteins...
January 4, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29303998/linking-dna-damage-and-age-related-promoter-dna-hyper-methylation-in-the-intestine
#6
Torsten Thalheim, Maria Herberg, Joerg Galle
Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Here, we explore whether and how DNA damage repair might impact on these time-dependent changes, in particular in proliferative intestinal stem cells. We introduce a 3D multiscale computer model of intestinal crypts enabling simulation of aberrant DNA and histone methylation of gene promoters during aging. We assume histone state-dependent activity of de novo DNA methyltransferases (DNMTs) and methylation-dependent binding of maintenance DNMTs to CpGs...
January 5, 2018: Genes
https://www.readbyqxmd.com/read/29299160/detection-of-prognostic-methylation-markers-by-methylc-capture-sequencing-in-acute-myeloid-leukemia
#7
Yan Li, Hongmei Zhao, Qingyu Xu, Na Lv, Yu Jing, Lili Wang, Xiaowen Wang, Jing Guo, Lei Zhou, Jing Liu, Guofeng Chen, Chongjian Chen, Yonghui Li, Li Yu
Clinical and genetic features incompletely predict outcome in acute myeloid leukemia (AML). The value of clinical methylation assays for prognostic markers has not been extensively explored. We assess the prognostic implications of methylC-capture sequencing (MCC-Seq) in patients with de novo AML by integrating DNA methylation and genetic risk stratification. MCC-Seq assessed DNA methylation level in 44 samples. The differentially methylated regions associated with prognostic genetic information were identified...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288197/recruitment-and-allosteric-stimulation-of-a-histone-deubiquitinating-enzyme-during-heterochromatin-assembly
#8
Alexis Zukowksi, Nouf Omar Al-Afaleq, Emily D Duncan, Tingting Yao, Aaron M Johnson
Heterochromatin formation in budding yeast is regulated by the silent information regulator (SIR) complex. The SIR complex comprises the NAD-dependent deacetylase Sir2, the scaffolding protein Sir4, and the nucleosome-binding protein Sir3. Transcriptionally active regions present a challenge to SIR complex-mediated de novo heterochromatic silencing due to the presence of antagonistic histone PTMs, including acetylation and methylation. Methylation of histone H3K4 and H3K79 are dependent on mono-ubiquitination of histone H2B (H2B-Ub)...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29244186/independence-between-pre-mrna-splicing-and-dna-methylation-in-an-isogenic-minigene-resource
#9
Kyster K Nanan, Cody Ocheltree, David Sturgill, Mariana D Mandler, Maria Prigge, Garima Varma, Shalini Oberdoerffer
Actively transcribed genes adopt a unique chromatin environment with characteristic patterns of enrichment. Within gene bodies, H3K36me3 and cytosine DNA methylation are elevated at exons of spliced genes and have been implicated in the regulation of pre-mRNA splicing. H3K36me3 is further responsive to splicing, wherein splicing inhibition led to a redistribution and general reduction over gene bodies. In contrast, little is known of the mechanisms supporting elevated DNA methylation at actively spliced genic locations...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29236683/effector-cd8-t-cells-dedifferentiate-into-long-lived-memory-cells
#10
Ben Youngblood, J Scott Hale, Haydn T Kissick, Eunseon Ahn, Xiaojin Xu, Andreas Wieland, Koichi Araki, Erin E West, Hazem E Ghoneim, Yiping Fan, Pranay Dogra, Carl W Davis, Bogumila T Konieczny, Rustom Antia, Xiaodong Cheng, Rafi Ahmed
Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29203910/tet-proteins-safeguard-bivalent-promoters-from-de-novo-methylation-in-human-embryonic-stem-cells
#11
Nipun Verma, Heng Pan, Louis C Doré, Abhijit Shukla, Qing V Li, Bobbie Pelham-Webb, Virginia Teijeiro, Federico González, Andrei Krivtsov, Chan-Jung Chang, Eirini P Papapetrou, Chuan He, Olivier Elemento, Danwei Huangfu
TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state...
January 2018: Nature Genetics
https://www.readbyqxmd.com/read/29203909/dynamic-epigenomic-landscapes-during-early-lineage-specification-in-mouse-embryos
#12
Yu Zhang, Yunlong Xiang, Qiangzong Yin, Zhenhai Du, Xu Peng, Qiujun Wang, Miguel Fidalgo, Weikun Xia, Yuanyuan Li, Zhen-Ao Zhao, Wenhao Zhang, Jing Ma, Feng Xu, Jianlong Wang, Lei Li, Wei Xie
In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29199514/rna-polymerases-iv-and-v-influence-the-3-boundaries-of-polymerase-ii-transcription-units-in-arabidopsis
#13
Anastasia McKinlay, Ram Podicheti, Jered M Wendte, Ross Cocklin, Douglas B Rusch
Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in plants as specialized forms of Pol II. Their functions are best understood in the context of RNA-directed DNA methylation (RdDM), a process in which Pol IV-dependent 24 nt siRNAs direct the de novo cytosine methylation of regions transcribed by Pol V. Pol V has additional functions, independent of Pol IV and 24 nt siRNA biogenesis, in maintaining the repression of transposons and genomic repeats whose silencing depends on maintenance cytosine methylation...
December 4, 2017: RNA Biology
https://www.readbyqxmd.com/read/29179494/combinatorial-effects-of-an-epigenetic-inhibitor-and-ionizing-radiation-contribute-to-targeted-elimination-of-pancreatic-cancer-stem-cell
#14
Hyun-Mi Kwon, Eun-Jin Kang, Keunsoo Kang, Sung-Dae Kim, Kwangmo Yang, Joo Mi Yi
Pancreatic cancer is associated with a high mortality rate, owing to de novo and acquired drug resistance, thereby leading to highly invasive and metastatic pancreatic cancer cells. Therefore, targeting pancreatic cancer stem cells (CSCs) may be a novel therapeutic strategy for the treatment of pancreatic cancer. Here, we combined a DNA methylation inhibitor (5-aza-2'-deoxycytidine; 5-aza-dC) and ionizing radiation (IR) to improve anti-cancer effects by inhibiting growth and proliferation and promoting apoptosis of pancreatic cancer cells in vitro and in vivo...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29164502/superovulation-alters-dna-methyltransferase-protein-expression-in-mouse-oocytes-and-early-embryos
#15
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
PURPOSE: DNA methylation is an epigenetic mechanism that plays critical roles during mammalian oocyte and preimplantation embryo development. It is achieved by adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites using DNA methyltransferase (DNMT) enzymes for de novo and maintenance methylation processes. DNMT1, DNMT3A, and DNMT3B play important roles in establishing methylation of developmentally related genes in oocytes and early embryos...
November 22, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29147493/the-effect-of-the-ovarian-varicose-vein-on-the-dna-methylation-in-the-rat-s-oocyte
#16
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
#17
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
#18
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
#19
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
#20
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
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