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https://www.readbyqxmd.com/read/28894287/prognostic-significance-of-high-gfi1-expression-in-aml-of-normal-karyotype-and-its-association-with-a-flt3-itd-signature
#1
Giacomo Volpe, David S Walton, David E Grainger, Carl Ward, Pierre Cauchy, Daniel Blakemore, Daniel J L Coleman, Peter N Cockerill, Paloma Garcia, Jon Frampton
Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820654/locus-specific-dna-methylation-in-the-placenta-is-associated-with-levels-of-pro-inflammatory-proteins-in-cord-blood-and-they-are-both-independently-affected-by-maternal-smoking-during-pregnancy
#2
Sanne D van Otterdijk, Alexandra M Binder, Karin B Michels
We investigated the impact of maternal smoking during pregnancy on placental DNA methylation and how this may mediate the association between maternal smoking and pro-inflammatory proteins in cord blood. The study population consisted of 27 individuals exposed to maternal smoking throughout pregnancy, 32 individuals exposed during a proportion of the pregnancy, and 61 unexposed individuals. Methylation of 11 regions within 6 genes in placenta tissue was assessed by pyrosequencing. Levels of 7 pro-inflammatory proteins in cord blood were assessed by electrochemiluminescence...
August 18, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28801480/gfi1-functions-in-transcriptional-control-and-cell-fate-determination-require-snag-domain-methylation-to-recruit-lsd1
#3
Matthew Velinder, Jason Singer, Diana Bareyan, Jessica Meznarich, Christopher M Tracy, James M Fulcher, David McClellan, Helena Lucente, Sarah Franklin, Sunil Sharma, Michael E Engel
No abstract text is available yet for this article.
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28662467/locus-specific-dna-methylation-changes-and-phenotypic-variability-in-children-with-attention-deficit-hyperactivity-disorder
#4
Sarojini M Sengupta, Alicia K Smith, Natalie Grizenko, Ridha Joober
Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy...
June 20, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28574132/mirna-650-exerts-anti-leukemia-activity-by-inhibiting-cell-proliferation-through-gfi1-targeting
#5
Changyong Yuan, Liming Xu, Pengcheng Du, Jinling Pang
BACKGROUND: Acute myeloid leukemia (AML) is the most common malignancy of the bone marrow with a high mortality. Recent advances in high-throughput sequencing have led to the identification of various miRNAs implicated in the pathogenesis of AML. We found in this study that miR-650, a miRNA that was traditionally considered to participate in the onset of hepatocellular carcinoma, might play a significant role in AML development and progression. METHODS: qRT-PCR was used to detect the expression of miR-650 and Gfi1 in AML patients and healthy controls...
May 26, 2017: Tumori
https://www.readbyqxmd.com/read/28514438/conversion-of-adult-endothelium-to-immunocompetent-haematopoietic-stem-cells
#6
Raphael Lis, Charles C Karrasch, Michael G Poulos, Balvir Kunar, David Redmond, Jose G Barcia Duran, Chaitanya R Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, Arash Rafii Tabrizi, Koji Shido, Zev Rosenwaks, Olivier Elemento, Nancy A Speck, Jason M Butler, Joseph M Scandura, Shahin Rafii
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28494218/maternal-cigarette-smoking-during-pregnancy-and-offspring-dna-methylation-in-midlife
#7
Parisa Tehranifar, Hui-Chen Wu, Jasmine A McDonald, Farzana Jasmine, Regina M Santella, Irina Gurvich, Julie D Flom, Mary Beth Terry
Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959-1964 and measured DNA methylation measured in blood (granulocytes) collected in 2001-2007 (mean age: 43 years)...
May 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28401061/transcription-factor-gfi1b-in-health-and-disease
#8
REVIEW
Eduardo Anguita, Francisco J Candel, Alberto Chaparro, Juan J Roldán-Etcheverry
Many human diseases arise through dysregulation of genes that control key cell fate pathways. Transcription factors (TFs) are major cell fate regulators frequently involved in cancer, particularly in leukemia. The GFI1B gene, coding a TF, was identified by sequence homology with the oncogene growth factor independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is essential for neutrophil differentiation in mice...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28387757/gfi1-downregulation-promotes-inflammation-linked-metastasis-of-colorectal-cancer
#9
Wenjing Xing, Yun Xiao, Xinliang Lu, Hongyan Zhu, Xiangchuan He, Wei Huang, Elsa S Lopez, Jerry Wong, Huanyu Ju, Linlu Tian, Fengmin Zhang, Hongwei Xu, Sheng Dian Wang, Xia Li, Michael Karin, Huan Ren
Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread...
May 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28337051/a-novel-cd48-based-analysis-of-sepsis-induced-mouse-myeloid-derived-suppressor-cell-compartments
#10
Bei Jia, Chenchen Zhao, Guoli Li, Yaxian Kong, Yaluan Ma, Qiuping Wang, Beibei Wang, Hui Zeng
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells that expands dramatically in many disease states and can suppress T-cell responses. MDSCs mainly include monocytic and granulocytic subpopulations that can be distinguished in mice by the expression of Ly6G and Ly6C cell surface markers. This identification system has been validated in experimental tumor models, but not in models of inflammation-associated conditions such as sepsis. We challenged growth factor independent 1 transcription repressor green fluorescent protein (Gfi1:GFP) knock-in reporter mice with cecal ligation and puncture surgery and found that CD11b(+)Ly6G(low)Ly6C(high) MDSCs in this sepsis model comprised both monocytic and granulocytic MDSCs...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28329683/inactivation-of-ezh2-upregulates-gfi1-and-drives-aggressive-myc-driven-group-3-medulloblastoma
#11
BaoHan T Vo, Chunliang Li, Marc A Morgan, Ilan Theurillat, David Finkelstein, Shaela Wright, Judith Hyle, Stephanie M C Smith, Yiping Fan, Yong-Dong Wang, Gang Wu, Brent A Orr, Paul A Northcott, Ali Shilatifard, Charles J Sherr, Martine F Roussel
The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#12
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28181545/gfi1-cre-mice-have-early-onset-progressive-hearing-loss-and-induce-recombination-in-numerous-inner-ear-non-hair-cells
#13
Maggie Matern, Sarath Vijayakumar, Zachary Margulies, Beatrice Milon, Yang Song, Ran Elkon, Xiaoyu Zhang, Sherri M Jones, Ronna Hertzano
Studies of developmental and functional biology largely rely on conditional expression of genes in a cell type-specific manner. Therefore, the importance of specificity and lack of inherent phenotypes for Cre-driver animals cannot be overemphasized. The Gfi1(Cre) mouse is commonly used for conditional hair cell-specific gene deletion/reporter gene activation in the inner ear. Here, using immunofluorescence and flow cytometry, we show that the Gfi1(Cre) mice produce a pattern of recombination that is not strictly limited to hair cells within the inner ear...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119431/ezh2-or-hdac1-inhibition-reverses-multiple-myeloma-induced-epigenetic-suppression-of-osteoblast-differentiation
#14
Juraj Adamik, Shunqian Jin, Quanhong Sun, Peng Zhang, Kurt R Weiss, Judith L Anderson, Rebecca Silbermann, G David Roodman, Deborah L Galson
In multiple myeloma, osteolytic lesions rarely heal because of persistent suppressed osteoblast differentiation resulting in a high fracture risk. Herein, chromatin immunoprecipitation analyses reveal that multiple myeloma cells induce repressive epigenetic histone changes at the Runx2 locus that prevent osteoblast differentiation. The most pronounced multiple myeloma-induced changes were at the Runx2-P1 promoter, converting it from a poised bivalent state to a repressed state. Previously, it was observed that multiple myeloma induces the transcription repressor GFI1 in osteoblast precursors, which correlates with decreased Runx2 expression, thus prompting detailed characterization of the multiple myeloma and TNFα-dependent GFI1 response element within the Runx2-P1 promoter...
April 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27994150/gfi1-foxo1-axis-controls-the-fidelity-of-effector-gene-expression-and-developmental-maturation-of-thymocytes
#15
Lewis Zhichang Shi, Jordy Saravia, Hu Zeng, Nishan S Kalupahana, Clifford S Guy, Geoffrey Neale, Hongbo Chi
Double-positive (DP) thymocytes respond to intrathymic T-cell receptor (TCR) signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these well-characterized events is the acquisition of a mature T-cell gene expression program characterized by the induction of the effector molecules IL-7Rα, S1P1, and CCR7, but the underlying mechanism remains elusive. We report here that transcription repressor Growth factor independent 1 (Gfi1) orchestrates the fidelity of the DP gene expression program and developmental maturation into SP cells...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27935972/distinct-epigenetic-effects-of-tobacco-smoking-in-whole-blood-and-among-leukocyte-subtypes
#16
Dan Su, Xuting Wang, Michelle R Campbell, Devin K Porter, Gary S Pittman, Brian D Bennett, Ma Wan, Neal A Englert, Christopher L Crowl, Ryan N Gimple, Kelly N Adamski, Zhiqing Huang, Susan K Murphy, Douglas A Bell
Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking-associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p <1...
2016: PloS One
https://www.readbyqxmd.com/read/27898587/maternal-epigenetics-and-fetal-and-neonatal-growth
#17
Sofia Kitsiou-Tzeli, Maria Tzetis
PURPOSE OF REVIEW: The article provides an update on new insights of factors altering inherited maternal epigenome that ultimately affect fetal and neonatal growth. RECENT FINDINGS: A number of new publications have identified mechanisms through which maternal nutrition, environmental exposures such as stress and toxic substances altering expression of imprinted genes during pregnancy can influence fetal and neonatal phenotype and susceptibility to disease development later in life...
February 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27887572/maternal-smoking-impacts-key-biological-pathways-in-newborns-through-epigenetic-modification-in-utero
#18
Daniel M Rotroff, Bonnie R Joubert, Skylar W Marvel, Siri E Håberg, Michael C Wu, Roy M Nilsen, Per M Ueland, Wenche Nystad, Stephanie J London, Alison Motsinger-Reif
BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine...
November 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#19
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27820734/the-role-of-the-transcriptional-repressor-growth-factor-independent-1-in-the-formation-of-myeloid-cells
#20
Jennifer Fraszczak, Tarik Möröy
PURPOSE OF REVIEW: Growth factor independent 1 (Gfi1) is a transcriptional repressor that plays multiple roles during myeloid commitment and development. Gfi1-deficient mice lack granulocytes, accumulate aberrant monocytes and show a hyperactivity of macrophages toward bacterial cell wall components. Since these initial findings, numerous additional studies have confirmed the role of Gfi1 in myeloid differentiation from hematopoietic stem cells and multipotent progenitors to bipotential lymphoid/myeloid precursors and myeloid effector cells...
January 2017: Current Opinion in Hematology
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