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https://www.readbyqxmd.com/read/28337051/a-novel-cd48-based-analysis-of-sepsis-induced-mouse-myeloid-derived-suppressor-cell-compartments
#1
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
#2
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
#3
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
#4
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
#5
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...
January 23, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27751776/atoh1-in-sensory-hair-cell-development-constraints-and-cofactors
#12
Aida Costa, Lynn M Powell, Sally Lowell, Andrew P Jarman
The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum...
October 14, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27677632/sudden-infant-death-syndrome-exposure-to-cigarette-smoke-leads-to-hypomethylation-upstream-of-the-growth-factor-independent-1-gfi1-gene-promoter
#13
Kristina Schwender, Hannah Holtkötter, Kristina Schulze Johann, Alina Glaub, Marianne Schürenkamp, Ulla Sibbing, Sabrina Banken, Mechtild Vennemann, Heidi Pfeiffer, Marielle Vennemann
PURPOSE: Smoking during pregnancy has long been known as an important risk factor for sudden infant death syndrome (SIDS). However, the precise relationship between the smoking behavior of the mother and SIDS still remains unclear. In this study, the influence of prenatal smoking exposure on the childrens' DNA methylation state of a CpG island located upstream of the promoter of the growth factor independent 1 (GFI1) gene was analyzed. METHODS: Blood samples of well-defined SIDS cases with non-smoking mothers (n = 11), SIDS cases with smoking mothers during pregnancy (n = 11), and non-SIDS cases (n = 6) were obtained from a previous study and methylation states were determined by bisulfite sequencing...
December 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/27600904/the-transcriptional-repressor-gfi1-prevents-lupus-autoimmunity-by-restraining-tlr7-signaling
#14
Benoit Desnues, Amanda B Macedo, Diana Ordoñez-Rueda, Annie Roussel-Queval, Bernard Malissen, Pierre Bruhns, Marie Malissen, Lena Alexopoulou
The transcriptional repressor growth factor independence 1 (Gfi1) is important in myeloid and lymphoid differentiation. In the current study we evaluated the involvement of Gfi1 in systemic lupus erythematosus (SLE). We found that Genista mice, which carry a hypomorphic mutation in the gfi1 gene or Gfi1-deficient (Gfi1(-/-) ) mice develop signs of spontaneous lupus autoimmunity, including increased serum levels of IgM and IgG2a, autoantibodies against RNA and DNA, glomerular immunodeposits and increased frequencies of plasmablasts, germinal center (GC) B cells and age-associated B cells (ABCs)...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27592349/the-promoter-and-multiple-enhancers-of-the-pou4f3-gene-regulate-expression-in-inner-ear-hair-cells
#15
Masatsugu Masuda, Yan Li, Kwang Pak, Eduardo Chavez, Lina Mullen, Allen F Ryan
Few enhancers that target gene expression to inner ear hair cells (HCs) have been identified. Using transgenic analysis of enhanced green fluorescent protein (eGFP) reporter constructs and bioinformatics, we evaluated the control of pou4f3 gene expression, since it is expressed only in HCs within the inner ear and continues to be expressed throughout life. An 8.5-kb genomic DNA fragment 5' to the start codon, containing three regions of high cross-species homology, drove expression in all embryonic and neonatal HCs, and adult vestibular and inner HCs, but not adult outer HCs...
September 3, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27580035/single-cell-analysis-of-mixed-lineage-states-leading-to-a-binary-cell-fate-choice
#16
Andre Olsson, Meenakshi Venkatasubramanian, Viren K Chaudhri, Bruce J Aronow, Nathan Salomonis, Harinder Singh, H Leighton Grimes
Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators. Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level...
September 29, 2016: Nature
https://www.readbyqxmd.com/read/27576864/dissecting-the-pre-placodal-transcriptome-to-reveal-presumptive-direct-targets-of-six1-and-eya1-in-cranial-placodes
#17
Nick Riddiford, Gerhard Schlosser
The pre-placodal ectoderm, marked by the expression of the transcription factor Six1 and its co-activator Eya1, develops into placodes and ultimately into many cranial sensory organs and ganglia. Using RNA-Seq in Xenopus laevis we screened for presumptive direct placodal target genes of Six1 and Eya1 by overexpressing hormone-inducible constructs of Six1 and Eya1 in pre-placodal explants, and blocking protein synthesis before hormone-inducing nuclear translocation of Six1 or Eya1. Comparing the transcriptome of explants with non-induced controls, we identified hundreds of novel Six1/Eya1 target genes with potentially important roles for placode development...
August 31, 2016: ELife
https://www.readbyqxmd.com/read/27500495/brpf1-is-essential-for-development-of-fetal-hematopoietic-stem-cells
#18
Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27493699/tobacco-smoking-differently-influences-cell-types-of-the-innate-and-adaptive-immune-system-indications-from-cpg-site-methylation
#19
Mario Bauer, Beate Fink, Loreen Thürmann, Markus Eszlinger, Gunda Herberth, Irina Lehmann
BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. RESULTS: Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86...
2015: Clinical Epigenetics
https://www.readbyqxmd.com/read/27467586/threshold-levels-of-gfi1-maintain-e2a-activity-for-b-cell-commitment-via-repression-of-id1
#20
Jennifer Fraszczak, Anne Helness, Riyan Chen, Charles Vadnais, François Robert, Cyrus Khandanpour, Tarik Möröy
A regulatory circuit that controls myeloid versus B lymphoid cell fate in hematopoietic progenitors has been proposed, in which a network of the transcription factors Egr1/2, Nab, Gfi1 and PU.1 forms the core element. Here we show that a direct link between Gfi1, the transcription factor E2A and its inhibitor Id1 is a critical element of this regulatory circuit. Our data suggest that a certain threshold of Gfi1 is required to gauge E2A activity by adjusting levels of Id1 in multipotent progenitors, which are the first bipotential myeloid/lymphoid-restricted progeny of hematopoietic stem cells...
2016: PloS One
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