Read by QxMD icon Read


Allison B Norvil, Christopher J Petell, Lama Abdullah Alabdi, Lanchen Wu, Sandra Rossie, Humaira Gowher
The catalytic domains of the de novo DNA methyltransferases, Dnmt3a-C and Dnmt3b-C are highly homologous. However their unique biochemical properties could potentially contribute to differences in the substrate preferences or biological functions of these enzymes. Dnmt3a-C forms tetramers through interactions at the dimer interface, which also promote multimerization on DNA and cooperativity. Similar to processive enzymes, cooperativity allows Dnmt3a-C to methylate multiple sites on the same DNA molecule, however it is unclear whether Dnmt3b-C methylates DNA by cooperative or processive mechanism...
October 21, 2016: Biochemistry
Hai-Qiang Dai, Bang-An Wang, Lu Yang, Jia-Jia Chen, Guo-Chun Zhu, Mei-Ling Sun, Hao Ge, Rui Wang, Deborah L Chapman, Fuchou Tang, Xin Sun, Guo-Liang Xu
Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined. Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling...
October 19, 2016: Nature
Wei Lu, Tanmin Lu, Xin Wei
In the present study, DNA (cytosine-5)-methyltransferase 3α (DNMT3a) is explored as an anticancer molecule in ovarian cancer treatment, and also the mechanistic link between DNMT3a and its regulatory signaling pathway in Caov-3 cells is provided. Firstly, DNMT3a protein expression in 12 freshly resected ovarian cancer patient tissues and tisssues from 8 ovariectomized patients was assessed. In the ovarian cancer tissues, DNMT3a expression was upregulated and miR-182 expression was downregulated. DNMT3a overexpression inhibited miR-182 expression and caspase-3 and -9 activity and suppressed p53 and c-Myc protein expression in Caov-3 cells...
September 28, 2016: Oncology Reports
Yuan-Yuan Zhang, Si-Han Huang, Hua-Rong Zhou, Cong-Jie Chen, Li-Hong Tian, Jian-Zhen Shen
HOX antisense intergenic RNA (HOTAIR), a long non-coding RNA, plays an important role in the development of many types of cancers. Its function in acute leukemia (AL), however, has not been examined. The present study investigated the role of HOTAIR and its downstream genes in AL, and determined whether it could act as a molecular marker for prediction of leukemia development and prognosis. Real-time quantitative PCR was used to examine the expression of each gene in the HOTAIR signaling pathway in AL patients...
October 4, 2016: Oncology Reports
María Abáigar, Cristina Robledo, Rocío Benito, Fernando Ramos, María Díez-Campelo, Lourdes Hermosín, Javier Sánchez-Del-Real, Jose M Alonso, Rebeca Cuello, Marta Megido, Juan N Rodríguez, Guillermo Martín-Núñez, Carlos Aguilar, Manuel Vargas, Ana A Martín, Juan L García, Alexander Kohlmann, M Consuelo Del Cañizo, Jesús M Hernández-Rivas
To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases...
2016: PloS One
Zhiying Luo, Xi Li, Mingfeng Zhu, Jie Tang, Zhi Li, Xinming Zhou, Guobao Song, Zhaoqian Liu, Honghao Zhou, Wei Zhang
BACKGROUND: The variation among patients in warfarin response complicated the management of warfarin therapy, improper therapeutic dose usually result in serious adverse events. OBJECTIVE: A two-stage extreme phenotype strategy was conducted to discover novel warfarin dose associated mutations in heart valve replacement (HVR) patients. PATIENTS/METHOD: A total of 1617 warfarin stable dose (WSD) patients were enrolled and divided randomly into two cohorts...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
E Balada, L Felip, J Ordi-Ros, M Vilardell-Tarrés
We evaluated the transcriptional expression of DUSP23 in CD4+ T cells from 30 SLE patients and 30 healthy controls. DUSP23 mRNA levels were considerably higher in the patients group: 1,490 ± 1,713 versus 294,1 ± 204,2. None association was found between DUSP23 mRNA expression and the presence of typical serological and clinical parameters associated to SLE. Meaningful statistical values were obtained in the patients group between the levels of DUSP23 and ITGAL, PRF1, and CD40L. Similarly, transcript levels of different DNA methylation-related enzymes (DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4) were also positively correlated to the expression of DUSP23...
October 13, 2016: Clinical and Experimental Immunology
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n=261). DNMT3A mutations were seen in 6% (n=16); 56% (n=9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients...
October 12, 2016: American Journal of Hematology
Hideaki Nakajima
Epigenetic marks, such as histone modifications or DNA methylation, regulate tissue specific gene expression by affecting the structures and accessibility of chromatin or DNA. Epigenetics, the molecular mechanisms regulating the epigenome, would therefore be critically involved in development and cell differentiation versus proliferation. Histone modifications include methylation, acetylation, phosphorylation and ubiquitination of specific lysine, arginine or serine residues on histone tails, and each modification has its own specific effect on gene expressions...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Jie Xu, Wu Zhang, Xiao-Jing Yan, Xue-Qiu Lin, Wei Li, Jian-Qing Mi, Jun-Min Li, Jiang Zhu, Zhu Chen, Sai-Juan Chen
BACKGROUND: DNMT3A mutations are frequently discovered in acute myeloid leukemia (AML), associated with poor outcome. Recently, a relapse case report of AML extramedullary disease has showed that AML cells harboring DNMT3A variation were detected in the cerebral spinal fluid. However, whether a causal relationship exists between DNMT3A mutation (D3Amut) and extramedullary infiltration (EMI) is unclear. METHODS: We took advantage of DNMT3A (R882C) mutation-carrying AML cell strain, that is, OCI-AML3, assessing its migration ability in vitro and in vivo...
October 10, 2016: Journal of Hematology & Oncology
Jakob Werner Hansen, Maj Karoline Westman, Lene Dissing Sjö, Lenonie Saft, Lasse Sommer Kristensen, Andreas Due Ørskov, Marianne Treppendahl, Mette Klarskov Andersen, Kirsten Grønbaek
Cytopenia is common in the elderly population and etiology may be difficult to assess. Here, we investigated the occurrence of mutations in patients with idiopathic cytopenia of undetermined significance and the usefulness in improving diagnostics. We included 60 patients with persistent cytopenia > 6 months without definite diagnosis of hematological neoplasm after routine assessment. Bone marrow material underwent a blinded morphology review and DNA was sequenced with a targeted 20 gene panel representing the most commonly mutated genes in myelodysplastic syndrome...
September 15, 2016: American Journal of Hematology
Ying Wang, George L Sen
In this issue of Cell Stem Cell, Rinaldi et al. (2016) find an unexpected role for the de novo DNA methyltransferases Dnmt3a and Dnmt3b in the regulation of enhancers. Their findings provide new insight into how regulation of enhancer activity through DNA methylation can have dramatic consequences on epidermal stem cell fate decisions.
October 6, 2016: Cell Stem Cell
Baozhong Xin, Tania Cruz Marino, Julia Szekely, Josianne Leblanc, Karen Cechner, Valerie Sency, Christine Wensel, Melinda Barabas, Valérie Therriault, Heng Wang
Tatton-Brown-Rahman syndrome (TBRS) was recently described in 13 isolated cases with de novo mutations in the DNMT3A gene. This autosomal dominant condition is characterized by tall stature, intellectual disability and a distinctive facial appearance. Here, we report six cases of inherited TBRS caused by novel DNMT3A germline mutations. The affected individuals belong to two sib-ships: 4 from an Old Order Amish family in America and 2 from a French Canadian family in Canada. All of them presented with characteristic features of TBRS, including dysmorphic facial features, increased height, intellectual disability, and variable additional features...
October 4, 2016: Clinical Genetics
Xiaowu Zhong, Yuanhong Peng, Chengjiao Yao, Yufeng Qing, Qibin Yang, Xiaolan Guo, Wenguang Xie, Mingcai Zhao, Xiaoming Cai, Jing-Guo Zhou
Gouty arthritis is the most common type of inflammatory and immune disease, and the prevalence and incidence of gout increases annually. Genetic variations in the DNA methyltransferases (DNMTs) gene have not, to the best of our knowledge, been reported to influence gene expression and to participate in the pathogenesis of gout. The aim of the present study was to investigate whether the DNMT1, DNMT3A and DNMT3B polymorphisms contribute to gout susceptibility. These polymorphisms were screened for in 336 gout patients and 306 healthy control subjects (from a South China population) for association with gout...
October 2016: Biomedical Reports
Mathilde Cheray, Romain Pacaud, Arulraj Nadaradjane, Lisa Oliver, François M Vallette, Pierre-François Cartron
DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide)...
2016: Theranostics
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease...
September 27, 2016: Kidney International
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
Qin Yang, Maren J Pröll, Dessie Salilew-Wondim, Rui Zhang, Dawit Tesfaye, Huitao Fan, Mehmet U Cinar, Christine Große-Brinkhaus, Ernst Tholen, Mohammad A Islam, Michael Hölker, Karl Schellander, Muhammad J Uddin, Christiane Neuhoff
Pulmonary alveolar macrophages (AMs) are important in defense against bacterial lung inflammation. Cluster of differentiation 14 (CD14) is involved in recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the LPS-induced TRIF pathway, an AMs model was investigated in vitro CD14 gene expression was induced by 5 µg/ml LPS at the time point of 12 h and suppressed by 5 µM SFN...
September 29, 2016: Innate Immunity
Fatma Uysal, Gokhan Akkoyunlu, Saffet Ozturk
DNA methylation is one of the epigenetic marks and plays critically important functions during spermatogenesis in mammals. DNA methylation is catalysed by DNA methyltransferase (DNMT) enzymes, which are responsible for the addition of a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. Structurally and functionally five different DNMT enzymes have been identified in mammals, including DNMT1, DNMT2, DNMT3A, DNMT3B and DNMT3L...
September 12, 2016: Reproductive Biomedicine Online
Staci L Haney, Garland M Upchurch, Jana Opavska, David Klinkebiel, Adams Kusi Appiah, Lynette M Smith, Tayla B Heavican, Javeed Iqbal, Shantaram Joshi, Rene Opavsky
Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EμSRα-tTA;Teto-Cre;Dnmt3a(fl/fl); Rosa26LOXP(EGFP/EGFP) (Dnmt3a(Δ/Δ)) mice...
September 28, 2016: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"