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https://www.readbyqxmd.com/read/29751772/expression-profiling-of-cell-intrinsic-regulators-in-the-process-of-differentiation-of-human-ipscs-into-retinal-lineages
#1
Jen-Hua Chuang, Aliaksandr A Yarmishyn, De-Kuang Hwang, Chih-Chien Hsu, Mong-Lien Wang, Yi-Ping Yang, Ke-Hung Chien, Shih-Hwa Chiou, Chi-Hsien Peng, Shih-Jen Chen
BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages. METHODS: In this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29688344/dynamic-and-cell-specific-dach1-expression-in-human-neocortical-and-striatal-development
#2
Valentina Castiglioni, Andrea Faedo, Marco Onorati, Vittoria Dickinson Bocchi, Zhen Li, Raffaele Iennaco, Romina Vuono, Gaetano P Bulfamante, Luca Muzio, Gianvito Martino, Nenad Sestan, Roger A Barker, Elena Cattaneo
DACH1 is the human homolog of the Drosophila dachshund gene, which is involved in the development of the eye, nervous system, and limbs in the fly. Here, we systematically investigate DACH1 expression patterns during human neurodevelopment, from 5 to 21 postconceptional weeks. By immunodetection analysis, we found that DACH1 is highly expressed in the proliferating neuroprogenitors of the developing cortical ventricular and subventricular regions, while it is absent in the more differentiated cortical plate...
April 24, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29669755/zinc-finger-irf-composite-elements-bound-by-ikaros-irf4-complexes-function-as-gene-repression-in-plasma-cell
#3
Kyoko Ochiai, Haruka Kondo, Yasunobu Okamura, Hiroki Shima, Yuko Kurokochi, Kazumi Kimura, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Katsuyuki Yui, Kengo Kinoshita, Kazuhiko Igarashi
The transcription factor (TF) interferon regulatory factor-4 (IRF4) promotes both germinal center (GC) reactions and plasma cell (PC) differentiation by binding to alternative DNA motifs including AP-1-IRF composite elements, Ets-IRF composite elements (EICEs), and interferon sequence response elements (ISREs). Although all of these motifs mediate transcriptional activation by IRF4, it is still unknown how some of the IRF4 target genes are downregulated upon PC differentiation. Here, we revealed a molecular mechanism of IRF4-mediated gene downregulation during PC differentiation...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29643073/the-plant-hormone-ethylene-restricts-arabidopsis-growth-via-the-epidermis
#4
Irina Ivanova Vaseva, Enas Qudeimat, Thomas Potuschak, Yunlong Du, Pascal Genschik, Filip Vandenbussche, Dominique Van Der Straeten
The gaseous hormone ethylene plays a key role in plant growth and development, and it is a major regulator of stress responses. It inhibits vegetative growth by restricting cell elongation, mainly through cross-talk with auxins. However, it remains unknown whether ethylene controls growth throughout all plant tissues or whether its signaling is confined to specific cell types. We employed a targeted expression approach to map the tissue site(s) of ethylene growth regulation. The ubiquitin E3 ligase complex containing Skp1, Cullin1, and the F-box protein EBF1 or EBF2 (SCFEBF1/2 ) target the degradation of EIN3, the master transcription factor in ethylene signaling...
April 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29575541/simultaneous-detection-of-abl1-mutation-and-ikzf1-deletion-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-using-a-customized-target-enrichment-system-panel
#5
M Aoe, H Ishida, T Matsubara, S Karakawa, H Kawaguchi, K Fujiwara, K Kanamitsu, K Washio, K Okada, M Shibakura, A Shimada
INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary...
March 25, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29563184/stem-cell-niche-specific-ebf3-maintains-the-bone-marrow-cavity
#6
Masanari Seike, Yoshiki Omatsu, Hitomi Watanabe, Gen Kondoh, Takashi Nagasawa
Bone marrow is the tissue filling the space between bone surfaces. Hematopoietic stem cells (HSCs) are maintained by special microenvironments known as niches within bone marrow cavities. Mesenchymal cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-positive (LepR+ ) cells, are a major cellular component of HSC niches that gives rise to osteoblasts in bone marrow. However, it remains unclear how osteogenesis is prevented in most CAR/LepR+ cells to maintain HSC niches and marrow cavities...
March 21, 2018: Genes & Development
https://www.readbyqxmd.com/read/29552179/prognostic-significance-of-copy-number-alterations-detected-by-multi-link-probe-amplification-of-multiple-genes-in-adult-acute-lymphoblastic-leukemia
#7
Qiuyun Fang, Tian Yuan, Yan Li, Juan Feng, Xiaoyuan Gong, Qinghua Li, Xingli Zhao, Kaiqi Liu, Kejing Tang, Zheng Tian, Qi Zhang, Ying Wang, Bingcheng Liu, Min Wang, Kun Ru, Jianxiang Wang, Yingchang Mi
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 ( IKZF1 ), paired box 5 ( PAX5 ), ETS variant 6 ( ETV6 ), RB transcriptional corepressor 1 ( RB1 ), BTG anti-proliferation factor 1 ( BTG1 ), early B-cell factor 1 ( EBF1 ), cyclin dependent kinase inhibitor 2A/2B ( CDKN2A/2B ) and cytokine receptor like factor 2 ( CRLF2 ) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29498923/ikzf1-plus-defines-a-new-minimal-residual-disease-dependent-very-poor-prognostic-profile-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#8
Martin Stanulla, Elif Dagdan, Marketa Zaliova, Anja Möricke, Chiara Palmi, Giovanni Cazzaniga, Cornelia Eckert, Geertruy Te Kronnie, Jean-Pierre Bourquin, Beat Bornhauser, Rolf Koehler, Claus R Bartram, Wolf-Dieter Ludwig, Kirsten Bleckmann, Stefanie Groeneveld-Krentz, Denis Schewe, Stefanie V Junk, Laura Hinze, Norman Klein, Christian P Kratz, Andrea Biondi, Arndt Borkhardt, Andreas Kulozik, Martina U Muckenthaler, Giuseppe Basso, Maria Grazia Valsecchi, Shai Izraeli, Britt-Sabina Petersen, Andre Franke, Petra Dörge, Doris Steinemann, Oskar A Haas, Renate Panzer-Grümayer, Hélène Cavé, Richard S Houlston, Gunnar Cario, Martin Schrappe, Martin Zimmermann
Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22...
April 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29467311/epstein-barr-virus-nuclear-antigen-leader-protein-coactivates-ep300
#9
Chong Wang, Hufeng Zhou, Yong Xue, Jun Liang, Yohei Narita, Catherine Gerdt, Amy Y Zheng, Runsheng Jiang, Stephen Trudeau, Chih-Wen Peng, Benjamin E Gewurz, Bo Zhao
Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B-cell immortalization. EBNALP is thought to function primarily by coactivating EBNA2-mediated transcription. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) studies highlight that EBNALP frequently cooccupies DNA sites with host cell transcription factors (TFs), in particular, EP300, implicating a broader role in transcription regulation...
May 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29462212/epstein-barr-virus-nuclear-antigen-ebna-lp-is-essential-for-transforming-na%C3%A3-ve-b-cells-and-facilitates-recruitment-of-transcription-factors-to-the-viral-genome
#10
Agnieszka Szymula, Richard D Palermo, Amr Bayoumy, Ian J Groves, Mohammed Ba Abdullah, Beth Holder, Robert E White
The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of internal repeat 1 (IR1). EBNA-LP-mutant EBVs established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but not from umbilical cord B cells, which died approximately two weeks after infection...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29453396/bone-marrow-lympho-myeloid-malfunction-in-obesity-requires-precursor-cell-autonomous-tlr4
#11
Ailing Liu, Minhui Chen, Rashmi Kumar, Maja Stefanovic-Racic, Robert M O'Doherty, Ying Ding, Willi Jahnen-Dechent, Lisa Borghesi
Obesity, a prevalent condition in adults and children, impairs bone marrow (BM) function. However, the underlying mechanisms are unclear. Here, we show that obese mice exhibit poor emergency immune responses in a toll-like receptor 4 (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid bias arises after 6 weeks of high-fat diet and depends on precursor cell-autonomous TLR4...
February 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29440261/dynamic-ebf1-occupancy-directs-sequential-epigenetic-and-transcriptional-events-in-b-cell-programming
#12
Rui Li, Pierre Cauchy, Senthilkumar Ramamoorthy, Sören Boller, Lukas Chavez, Rudolf Grosschedl
B-cell fate determination requires the action of transcription factors that operate in a regulatory network to activate B-lineage genes and repress lineage-inappropriate genes. However, the dynamics and hierarchy of events in B-cell programming remain obscure. To uncouple the dynamics of transcription factor expression from functional consequences, we generated induction systems in developmentally arrested Ebf1 -/- pre-pro-B cells to allow precise experimental control of EBF1 expression in the genomic context of progenitor cells...
January 15, 2018: Genes & Development
https://www.readbyqxmd.com/read/29407587/high-frequency-of-intermediate-and-poor-risk-copy-number-abnormalities-in-pediatric-cohort-of-b-all-correlate-with-high-mrd-post-induction
#13
Minu Singh, Prateek Bhatia, Amita Trehan, Neelam Varma, Manupdesh Singh Sachdeva, Deepak Bansal, Richa Jain, Shano Naseem
Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29348129/genomic-cdkn2a-2b-deletions-in-adult-ph-all-are-adverse-despite-allogeneic-stem-cell-transplantation
#14
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)+ acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation (aSCT). Ninety-seven Ph+ ALL patients (median age 41 years; range 18-64 years) within the prospective multicenter German Multicenter ALL Study Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients received TKI and aSCT in first complete remission (CR1)...
March 29, 2018: Blood
https://www.readbyqxmd.com/read/29336845/defining-b-cell-chromatin-lessons-from-ebf1
#15
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...
April 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
#16
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 F A Grant, Thorkild I A 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 of birth weight have focused on fetal genetics, whereas 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...
February 15, 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
#17
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
#18
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
#19
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/comprehensive-proteomic-investigation-of-ebf1-heterozygosity-in-pro-b-lymphocytes-utilizing-data-independent-acquisition
#20
Yaarub R Musa, Sören 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 data independent acquisition (DIA) and shotgun data dependent acquisition (DDA) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells...
January 5, 2018: Journal of Proteome Research
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