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https://www.readbyqxmd.com/read/29348129/genomic-cdkn2a-2b-deletions-in-adult-ph-all-are-adverse-despite-allogeneic-stem-cell-transplantation
#1
Heike Pfeifer, Katharina Raum, Sandra Markovic, Verena Nowak, Stephanie Fey, Julia Obländer, Jovita Pressler, Verena Böhm, Monika Brüggemann, Lydia Wunderle, Andreas Hüttmann, Ralph Wäsch, Joachim Beck, Matthias Stelljes, Andreas Viardot, Fabian Lang, Dieter Hoelzer, Wolf-Karsten Hofmann, Hubert Serve, Christel Weiss, Nicola Goekbuget, Oliver G Ottmann, Daniel Nowak
We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ ALL treated with tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplantation (aSCT). 97 Ph+ ALL patients (median age 41 years, range 18-64 years) within the prospective multicenter GMALL studies 06/99 (n=8) and 07/2003 (n=89) were analysed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with SNP arrays and validated by multiplex ligation-dependent probe amplification (MLPA)...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29336845/defining-b-cell-chromatin-lessons-from-ebf1
#2
REVIEW
Sören Boller, Rui Li, Rudolf Grosschedl
Hematopoiesis is regulated by signals from the microenvironment, transcription factor networks, and changes of the epigenetic landscape. Transcription factors interact with and shape chromatin to allow for lineage- and cell type-specific changes in gene expression. During B lymphopoiesis, epigenetic regulation is observed in multilineage progenitors in which a specific chromatin context is established, at the onset of the B cell differentiation when early B cell factor 1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J recombination and after antigen-driven activation of B cells and terminal differentiation...
January 11, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29309628/genome-wide-association-study-of-offspring-birth-weight-in-86-577-women-identifies-five-novel-loci-and-highlights-maternal-genetic-effects-that-are-independent-of-fetal-genetics
#3
Robin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C Richmond, Lavinia Paternoster, Jonathan P Bradfield, Eskil Kreiner-Møller, Ville Huikari, Sarah Metrustry, Kathryn L Lunetta, Jodie N Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J Barton, Ana Espinosa, Julie A Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani Heikkinen, Øyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M Inskip, Samuel E Jones, Manolis Kogevinas, Penelope A Lind, Letizia Marullo, Sarah E Medland, Anna Murray, Jeffrey C Murray, Pål R Njølstad, Ellen A Nohr, Christoph Reichetzeder, Susan M Ring, Katherine S Ruth, Loreto Santa-Marina, Denise M Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A Tuke, Marc Vaudel, Michael N Weedon, Gonneke Willemsen, Andrew R Wood, Hanieh Yaghootkar, Louis J Muglia, Meike Bartels, Caroline L Relton, Craig E Pennell, Leda Chatzi, Xavier Estivill, John W Holloway, Dorret I Boomsma, Grant W Montgomery, Joanne M Murabito, Tim D Spector, Christine Power, Marjo-Ritta Järvelin, Hans Bisgaard, Struan Fa Grant, Thorkild Ia Sørensen, Vincent W Jaddoe, Bo Jacobsson, Mads Melbye, Mark I McCarthy, Andrew T Hattersley, M Geoffrey Hayes, Timothy M Frayling, Marie-France Hivert, Janine F Felix, Elina Hyppönen, William L Lowe, David M Evans, Debbie A Lawlor, Bjarke Feenstra, Rachel M Freathy
Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects...
January 3, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29284783/cd150-and-cd180-are-involved-in-regulation-of-transcription-factors-expression-in-chronic-lymphocytic-leukemia-cells
#4
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29213259/characterization-of-a-suppressive-cis-acting-element-in-the-epstein-barr-virus-lmp1-promoter
#5
Masahiro Yoshida, Takayuki Murata, Keiji Ashio, Yohei Narita, Takahiro Watanabe, H M Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura
Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein-Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29191698/micrornas-361-5p-and-mir-574-5p-associate-with-human-adipose-morphology-and-regulate-ebf1-expression-in-white-adipose-tissue
#6
Yasmina Belarbi, Niklas Mejhert, Hui Gao, Peter Arner, Mikael Rydén, Agné Kulyté
Reduced adipose expression of the transcription factor Early B cell factor 1 (EBF1) is linked to white adipose tissue (WAT) hypertrophy. We aimed to identify microRNAs (miRNAs) associated with WAT hypertrophy and EBF1 regulation. We mapped WAT miRNA expression from 26 non-obese women discordant in WAT morphology and determined EBF1 activity in the non-obese and 30 obese women. Expression of 15 miRNAs was higher in hypertrophy and 10 were predicted to target EBF1. Binding of miR-365-5p/miR-574-5p were validated with 3'-UTR assay...
November 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29181981/a-comprehensive-proteomic-investigation-of-ebf1-heterozygosity-in-pro-b-lymphocytes-utilizing-data-independent-acquisition-dia
#7
Yaarub Raji Musa, Soeren Boller, Monika Puchalska, Rudolf Grosschedl, Gerhard Mittler
Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells...
November 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29169115/prolonged-oxidative-stress-down-regulates-early-b-cell-factor-1-with-inhibition-of-its-tumor-suppressive-function-against-cholangiocarcinoma-genesis
#8
Napat Armartmuntree, Mariko Murata, Anchalee Techasen, Puangrat Yongvanit, Watcharin Loilome, Nisana Namwat, Chawalit Pairojkul, Chadamas Sakonsinsiri, Somchai Pinlaor, Raynoo Thanan
Early B cell factor 1 (EBF1) is a transcription factor involved in the differentiation of several stem cell lineages and it is a negative regulator of estrogen receptors. EBF1 is down-regulated in many tumors, and is believed to play suppressive roles in cancer promotion and progression. However, the functional roles of EBF1 in carcinogenesis are unclear. Liver fluke-infection-associated cholangiocarcinoma (CCA) is an oxidative stress-driven cancer of bile duct epithelium. In this study, we investigated EBF1 expression in tissues from CCA patients, CCA cell lines (KKU-213, KKU-214 and KKU-156), cholangiocyte (MMNK1) and its oxidative stress-resistant (ox-MMNK1-L) cell lines...
November 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/29133398/analysis-of-high-resolution-3d-intrachromosomal-interactions-aided-by-bayesian-network-modeling
#9
Xizhe Zhang, Sergio Branciamore, Grigoriy Gogoshin, Andrei S Rodin, Arthur D Riggs
Long-range intrachromosomal interactions play an important role in 3D chromosome structure and function, but our understanding of how various factors contribute to the strength of these interactions remains poor. In this study we used a recently developed analysis framework for Bayesian network (BN) modeling to analyze publicly available datasets for intrachromosomal interactions. We investigated how 106 variables affect the pairwise interactions of over 10 million 5-kb DNA segments in the B-lymphocyte cell line GB12878...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#10
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29097680/epigenome-wide-association-studies-identify-dna-methylation-associated-with-kidney-function
#11
Audrey Y Chu, Adrienne Tin, Pascal Schlosser, Yi-An Ko, Chengxiang Qiu, Chen Yao, Roby Joehanes, Morgan E Grams, Liming Liang, Caroline A Gluck, Chunyu Liu, Josef Coresh, Shih-Jen Hwang, Daniel Levy, Eric Boerwinkle, James S Pankow, Qiong Yang, Myriam Fornage, Caroline S Fox, Katalin Susztak, Anna Köttgen
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28982592/human-amyloid-%C3%AE-peptide-and-tau-co-expression-impairs-behavior-and-causes-specific-gene-expression-changes-in-caenorhabditis-elegans
#12
Chenyin Wang, Valeria Saar, Ka Lai Leung, Liang Chen, Garry Wong
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-β peptide (Aβ) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing Aβ1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans...
October 2, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28978690/aryl-hydrocarbon-receptor-activation-suppresses-ebf1-and-pax5-and-impairs-human-b-lymphopoiesis
#13
Jinpeng Li, Sudin Bhattacharya, Jiajun Zhou, Ashwini S Phadnis-Moghe, Robert B Crawford, Norbert E Kaminski
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates biological responses to endogenous and environmental chemical cues. Increasing evidence shows that the AHR plays physiological roles in regulating development, homeostasis, and function of a variety of cell lineages in the immune system. However, the role of AHR in human B cell development has not been investigated. Toward this end, an in vitro feeder-free human B cell developmental model system was employed using human cord blood CD34(+) hematopoietic stem/progenitor cells...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28977418/developmentally-regulated-higher-order-chromatin-interactions-orchestrate-b-cell-fate-commitment
#14
Ravi Boya, Anurupa Devi Yadavalli, Sameena Nikhat, Sreenivasulu Kurukuti, Dasaradhi Palakodeti, Jagan M R Pongubala
Genome organization in 3D nuclear-space is important for regulation of gene expression. However, the alterations of chromatin architecture that impinge on the B cell-fate choice of multi-potent progenitors are still unclear. By integrating in situ Hi-C analyses with epigenetic landscapes and genome-wide expression profiles, we tracked the changes in genome architecture as the cells transit from a progenitor to a committed state. We identified the genomic loci that undergo developmental switch between A and B compartments during B-cell fate determination...
August 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28968461/ebf1-binds-to-ebna2-and-promotes-the-assembly-of-ebna2-chromatin-complexes-in-b-cells
#15
Laura V Glaser, Simone Rieger, Sybille Thumann, Sophie Beer, Cornelia Kuklik-Roos, Dietmar E Martin, Kerstin C Maier, Marie L Harth-Hertle, Björn Grüning, Rolf Backofen, Stefan Krebs, Helmut Blum, Ralf Zimmer, Florian Erhard, Bettina Kempkes
Epstein-Barr virus (EBV) infection converts resting human B cells into permanently proliferating lymphoblastoid cell lines (LCLs). The Epstein-Barr virus nuclear antigen 2 (EBNA2) plays a key role in this process. It preferentially binds to B cell enhancers and establishes a specific viral and cellular gene expression program in LCLs. The cellular DNA binding factor CBF1/CSL serves as a sequence specific chromatin anchor for EBNA2. The ubiquitous expression of this highly conserved protein raises the question whether additional cellular factors might determine EBNA2 chromatin binding selectively in B cells...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#16
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28886309/the-correlation-between-pax5-deletion-and-patients-survival-in-iranian-children-with-precursor-b-cell-acute-lymphocytic-leukemia
#17
A Moafi, A Zojaji, R Salehi, S Najafi Dorcheh, S Rahgozar
Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012...
August 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28877031/genetic-associations-with-gestational-duration-and-spontaneous-preterm-birth
#18
Ge Zhang, Bjarke Feenstra, Jonas Bacelis, Xueping Liu, Lisa M Muglia, Julius Juodakis, Daniel E Miller, Nadia Litterman, Pan-Pan Jiang, Laura Russell, David A Hinds, Youna Hu, Matthew T Weirauch, Xiaoting Chen, Arun R Chavan, Günter P Wagner, Mihaela Pavličev, Mauris C Nnamani, Jamie Maziarz, Minna K Karjalainen, Mika Rämet, Verena Sengpiel, Frank Geller, Heather A Boyd, Aarno Palotie, Allison Momany, Bruce Bedell, Kelli K Ryckman, Johanna M Huusko, Carmy R Forney, Leah C Kottyan, Mikko Hallman, Kari Teramo, Ellen A Nohr, George Davey Smith, Mads Melbye, Bo Jacobsson, Louis J Muglia
BACKGROUND: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28860953/comparative-analyses-of-signature-genes-in-acute-rejection-and-operational-tolerance
#19
Jeong-Woo Choi, Yong-Hee Kim, Ji Won Oh
Using biomarkers as prediction tools or therapeutic targets can be a valuable strategy in transplantation. Recent studies identified biomarkers of acute rejection (AR) and operational tolerance (TOL) through the application of meta-analysis. In this study, we comparatively analyzed the signature genes in acute rejection and operational tolerance seen in human allogeneic transplantations using massive bioinformatical meta-analysis. To identify the signature genes in opposite immunological conditions, AR and TOL, we first collected the 1,252 gene expression data specifically intended for those circumstances...
August 2017: Immune Network
https://www.readbyqxmd.com/read/28794029/coordinate-regulation-of-tet2-and-ebna2-control-dna-methylation-state-of-latent-epstein-barr-virus
#20
Fang Lu, Andreas Wiedmer, Kayla A Martin, Priyankara J M S Wickramasinghe, Andrew V Kossenkov, Paul M Lieberman
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts...
August 9, 2017: Journal of Virology
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