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Dnmt3a

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https://www.readbyqxmd.com/read/29674693/methylation-associated-silencing-of-basp1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#1
Lei Zhou, Lin Fu, Na Lv, Jing Liu, Yan Li, Xiaosu Chen, Qingyu Xu, Guofeng Chen, Baoxu Pang, Lili Wang, Yonghui Li, Xiaodong Zhang, Li Yu
The AML1-ETO fusion protein (A/E), which results from the t(8;21) translocation, is considered to be a leukemia-initiating event. Identifying the mechanisms underlying the oncogenic activity of A/E remains a major challenge. In this study, we identified a specific down-regulation of brain acid-soluble protein 1 (BASP1) in t(8;21) acute myeloid leukemia (AML). A/E recognized AML1-binding sites and recruited DNA methyltransferase 3a (DNMT3a) to the BASP1 promoter sequence, which triggered DNA methylation-mediated silencing of BASP1...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29674125/deciphering-the-role-of-dimer-interface-in-intrinsic-dynamics-and-allosteric-pathways-underlying-the-functional-transformation-of-dnmt3a
#2
Zhongjie Liang, Junchi Hu, Wenying Yan, Hualiang Jiang, Guang Hu, Cheng Luo
BACKGROUND: DNMT3A, as de novo DNA methyltransferase, is essential for regulating gene expression through cellular development and differentiation. The functions of DNMT3A rely on its oligomeric states and allosteric regulations between its catalytic domain and binding partners. Despite recent resolution of autoinhibitory and active DNMT3A/3L crystal structures, the mechanism of their functional motions and interdomain allostery in regulating the activity remains to be established. METHODS: The hybrid approach, comprising Elastic Network Models coupled with information theory, Protein Structure Network, and sequence evolution analysis was employed to investigate intrinsic dynamics and allosteric properties of DNMT3A resolved in autoinhibitory and active states...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29669855/squalene-epoxidase-drives-nafld-induced-hepatocellular-carcinoma-and-is-a-pharmaceutical-target
#3
Dabin Liu, Chi Chun Wong, Li Fu, Huarong Chen, Liuyang Zhao, Chuangen Li, Yunfei Zhou, Yanquan Zhang, Weiqi Xu, Yidong Yang, Bin Wu, Gong Cheng, Paul Bo-San Lai, Nathalie Wong, Joseph J Y Sung, Jun Yu
Nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world; however, mechanisms that contribute to its formation are largely unknown, and targeted therapy is currently not available. Our RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase ( SQLE ) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Hepatocyte-specific Sqle transgenic expression in mice accelerated the development of high-fat, high-cholesterol diet-induced HCC...
April 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29666467/ascorbic-acid-induces-global-epigenetic-reprogramming-to-promote-meiotic-maturation-and-developmental-competence-of-porcine-oocytes
#4
Xiao-Xia Yu, Yun-Hua Liu, Xiao-Man Liu, Pei-Chao Wang, Shuai Liu, Jia-Kun Miao, Zhi-Qiang Du, Cai-Xia Yang
L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 μM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29662821/sperm-chromatin-and-dna-integrity-methyltransferase-mrna-levels-and-global-dna-methylation-in-oligoasthenoteratozoospermia
#5
Tahereh Rahiminia, Ehsan Farashahi Yazd, Farzaneh Fesahat, Mohammad Reza Moein, Ali Mohammad Mirjalili, Ali Reza Talebi
Objective: To investigate sperm chromatin/DNA integrity, global DNA methylation, and DNMT mRNA transcription in men with oligoasthenoteratozoospermia (OAT) compared with normozoospermic men. Methods: Semen samples from 32 OAT patients who comprised the case group and 32 normozoospermic men who comprised the control group were isolated and purified using a standard gradient isolation procedure according to World Health Organization criteria. DNMT1 , DNMT3A , and DNMT3B transcripts were then compared between groups using real-time quantitative reverse-transcription polymerase chain reaction...
March 2018: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/29662631/overlap-at-the-molecular-and-immunohistochemical-levels-between-angioimmunoblastic-t-cell-lymphoma-and-a-subgroup-of-peripheral-t-cell-lymphomas-without-specific-morphological-features
#6
Rebeca Manso, Julia González-Rincón, Manuel Rodríguez-Justo, Giovanna Roncador, Sagrario Gómez, Margarita Sánchez-Beato, Miguel A Piris, Socorro M Rodríguez-Pinilla
The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL ( TET2 , DNMT3A, IDH2, RHOA and PLCG1 ) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29660222/aberrant-methylation-of-eya4-promotes-epithelial-mesenchymal-transition-in-esophageal-squamous-cell-carcinoma
#7
Mei Luo, Yuan Li, Xuejiao Shi, Wenhui Yang, Fang Zhou, Nan Sun, Jie He
EYA4, one of the four members of the EYA gene family, is associated with several human cancers. However, its biological functions and molecular mechanisms in the progression of cancer, particularly in esophageal squamous cell carcinoma (ESCC), remain unknown. In the present study, we found that EYA4 was underexpressed and hypermethylated in most of the ESCC cell lines tested (85.7%, 6/7). Treatment with 5-aza-dC and/or TSA restored EYA4 expression in ESCC cell lines, which indicates that EYA4 expression was epigenetically regulated...
April 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29643943/-h19-overexpression-promotes-leukemogenesis-and-predicts-unfavorable-prognosis-in-acute-myeloid-leukemia
#8
Ting-Juan Zhang, Jing-Dong Zhou, Wei Zhang, Jiang Lin, Ji-Chun Ma, Xiang-Mei Wen, Qian Yuan, Xi-Xi Li, Zi-Jun Xu, Jun Qian
Background: The long non-coding RNA H19 plays a crucial role in solid tumor initiation and progression. However, the potential role of H19 and its clinical significance in acute myeloid leukemia (AML) remain largely elusive. Methods: H19 expression was detected by qPCR, and clinical significance in AML patients was further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data for AML were used as validation cohorts. The roles of H19 in cell proliferation and apoptosis were determined by cell proliferation assay and flow cytometry analysis...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29629950/a-survey-of-somatic-mutations-in-41-genes-in-a-cohort-of-t-cell-lymphomas-identifies-frequent-mutations-in-genes-involved-in-epigenetic-modification
#9
Sebastian Fernandez-Pol, Lisa Ma, Rohan P Joshi, Daniel A Arber
Here, we utilize a high throughput sequencing panel that covers several genes known to be recurrently mutated in certain T-cell lymphoma subtypes as well as genes frequently mutated in other hematolymphoid malignancies, including myeloid neoplasms. This panel was applied to formalin-fixed, paraffin-embedded tissue from 84 biopsies from 78 patients selected for this study. The biopsies included ones a with a diagnosis of T-cell lymphoma (n=79), including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n=26) and angioimmunoblastic T-cell lymphoma (AITL; n=13), as well as 5 cases of atypical T-cell proliferations...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29627222/lower-expression-of-bone-marrow-mir-122-is-an-independent-risk-factor-for-overall-survival-in-cytogenetically-normal-acute-myeloid-leukemia
#10
Ting-Juan Zhang, Zhen Qian, Xiang-Mei Wen, Jing-Dong Zhou, Xi-Xi Li, Zi-Jun Xu, Ji-Chun Ma, Zhi-Hui Zhang, Jiang Lin, Jun Qian
BACKGROUND: The liver-enriched microRNA-122 (miR-122) plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) with prognostic value. Recently, miR-122 was also found to be related to many other cancers besides HCC. However, less study determined miR-122 expression and its clinical significance in acute myeloid leukemia (AML). METHODS: Real-time quantitative PCR was performed to detect the level of bone marrow (BM) miR-122 in de novo AML patients. The clinical significance of miR-122 expression in AML was further investigated...
April 3, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29626481/nicotine-induces-aberrant-hypermethylation-of-tumor-suppressor-genes-in-pancreatic-epithelial-ductal-cells
#11
Tong Jin, Jianyu Hao, Daiming Fan
Tobacco smoking is an independent risk factor for the initiation of pancreatic cancer (PC). Hypermethylation of tumor suppressor genes has been demonstrated to be associated with smoking. This study aimed to find the relationship between nicotine exposure and hypermethylation of tumor suppressor genes in normal pancreatic epithelial cells. Human pancreatic epithelial cells ware cultured exposing to nicotine and the methylation status of tumor suppressor genes were detected. Proenkephalin (PENK) was chosen as the target gene and methylation level of PENK promoter region was measured...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29625060/de-novo-dna-methylation-marking-the-path-from-stem-cell-to-neural-fate
#12
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/29624746/hyperleukocytosis-is-associated-with-distinct-genetic-alterations-and-is-an-independent-poor-risk-factor-in-de-novo-acute-myeloid-leukemia-patients
#13
Feng-Ming Tien, Hsin-An Hou, Cheng-Hong Tsai, Jih-Luh Tang, Chien-Yuan Chen, Yuan-Yeh Kuo, Chi-Cheng Li, Chien-Ting Lin, Ming Yao, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Woei Tsay, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Wen-Chien Chou, Hwei-Fang Tien
OBJECTIVES: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited. METHODS: 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications...
April 6, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29621315/molecular-evolution-of-dnmt1-in-vertebrates-duplications-in-marsupials-followed-by-positive-selection
#14
David Alvarez-Ponce, María Torres-Sánchez, Felix Feyertag, Asmita Kulkarni, Taylen Nappi
DNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes three active Dnmts (Dnmt1, Dnmt3a and Dnmt3b), the tRNA methyltransferase Dnmt2, and the regulatory protein Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates...
2018: PloS One
https://www.readbyqxmd.com/read/29619748/association-of-gene-mutations-with-response-to-arsenic-containing-compound-qinghuang-powder-in-patients-with-myelodysplastic-syndromes
#15
Pan Zhao, Jun-Bin Liang, Zhong-Yang Deng, Ming-Jing Wang, Jia-Yue Qin, Chong-Jian Chen, Xiao-Mei Hu
OBJECTIVES: To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS). METHODS: Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed. RESULTS: Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation...
April 4, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29619119/dynamics-of-dnmt3a-mutation-and-prognostic-relevance-in-patients-with-primary-myelodysplastic-syndrome
#16
Ming-En Lin, Hsin-An Hou, Cheng-Hong Tsai, Shang-Ju Wu, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Wen-Chien Chou, Chien-Yuan Chen, Jih-Luh Tang, Ming Yao, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Chien-Ting Lin, Hwei-Fang Tien
Background: DNMT3A gene mutation has been associated with poor prognosis in acute myeloid leukemia, but its clinical implications in myelodysplastic syndrome (MDS) and dynamic changes during disease progression remain controversial. Results: In this study, DNMT3A mutation was identified in 7.9% of 469 de novo MDS patients. DNMT3A -mutated patients had higher platelet counts at diagnosis, and patients with ring sideroblasts had the highest incidence of DNMT3A mutations, whereas those with multilineage dysplasia had the lowest incidence...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29618722/incorporation-of-mutations-in-five-genes-in-the-revised-international-prognostic-scoring-system-can-improve-risk-stratification-in-the-patients-with-myelodysplastic-syndrome
#17
Hsin-An Hou, Cheng-Hong Tsai, Chien-Chin Lin, Wen-Chien Chou, Yuan-Yeh Kuo, Chieh-Yu Liu, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Ming Yao, Jih-Luh Tang, Hwei-Fang Tien
Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival...
April 4, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29617651/loss-of-dnmt3a-immortalizes-hematopoietic-stem-cells-in-vivo
#18
Mira Jeong, Hyun Jung Park, Hamza Celik, Elizabeth L Ostrander, Jaime M Reyes, Anna Guzman, Benjamin Rodriguez, Yong Lei, Yeojin Lee, Lei Ding, Olga A Guryanova, Wei Li, Margaret A Goodell, Grant A Challen
Somatic mutations in DNMT3A are recurrent events across a range of blood cancers. Dnmt3a loss of function in hematopoietic stem cells (HSCs) skews divisions toward self-renewal at the expense of differentiation. Moreover, DNMT3A mutations can be detected in the blood of aging individuals, indicating that mutant cells outcompete normal HSCs over time. It is important to understand how these mutations provide a competitive advantage to HSCs. Here we show that Dnmt3a-null HSCs can regenerate over at least 12 transplant generations in mice, far exceeding the lifespan of normal HSCs...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29614648/altered-microrna-mrna-and-protein-expression-of-neurodegeneration-related-biomarkers-and-their-transcriptional-and-epigenetic-modifiers-in-a-human-tau-transgenic-mouse-model-in-response-to-developmental-lead-exposure
#19
Anwar M Masoud, Syed W Bihaqi, Bothaina Alansi, Miriam Dash, Gehad M Subaiea, William E Renehan, Nasser H Zawia
Amyloid deposits originating from the amyloid-β protein precursor (AβPP) and aggregates of the microtubule associated protein tau (MAPT) are the hallmarks of Alzheimer's disease (AD). Animal studies have demonstrated a link between early life exposure to lead (Pb) and latent overexpression of the AβPP and MAPT genes and their products via epigenetic reprogramming. The present study monitored APP gene and epigenetic mediators and transcription factors known to regulate it. Western blot analysis and quantitative polymerase chain reaction (qPCR) were used to study the mRNA, miRNA, and proteins levels of AβPP, specificity protein 1 (SP1; a transcriptional regulator of amyloid and tau pathway), and epigenetic intermediates namely: DNA methyltransferase (DNMT) 1, DNMT3a and Methyl- CpG protein binding 2 (MeCP2) in the cerebral cortex of transgenic mice (Knock-in for human MAPT)...
March 28, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29603098/dna-methylation-of-genes-regulating-appetite-and-prediction-of-weight-loss-after-bariatric-surgery-in-obese-individuals
#20
F Coppedè, M Seghieri, A Stoccoro, E Santini, L Giannini, C Rossi, L Migliore, A Solini
PURPOSE: Epigenetic traits are influenced by clinical variables; interaction between DNA methylation (DNAmeth) and bariatric surgery-induced weight loss has been scarcely explored. We investigated whether DNAmeth of genes encoding for molecules/hormones regulating appetite, food intake or obesity could predict successful weight outcome following Roux-en-Y gastric bypass (RYGB). METHODS: Forty-five obese individuals with no known comorbidities were stratified accordingly to weight decrease one-year after RYGB (excess weight loss, EWL ≥ 50%: good responders, GR; EWL < 50%: worse responders, WR)...
March 30, 2018: Journal of Endocrinological Investigation
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