Genomes and Genes
Gene Symbol: Spi1
Description: spleen focus forming virus (SFFV) proviral integration oncogene
Alias: Dis-1, Dis1, PU.1, Sfpi-1, Sfpi1, Spi-1, Tcfpu1, Tfpu.1, transcription factor PU.1, 31 kDa-transforming protein, SFFV proviral integration 1 protein, hematopoietic transcription factor PU.1
- Medina K, Pongubala J, Reddy K, Lancki D, Dekoter R, Kieslinger M, et al. Assembling a gene regulatory network for specification of the B cell fate. Dev Cell. 2004;7:607-17 pubmed..1-/- or EBF-/- progenitors. Pax-5 expression and function are contingent on EBF. Based on these results, we propose a hierarchical regulatory network for specification and commitment to the B cell fate. ..
- Anderson K, Perkin H, Surh C, Venturini S, Maki R, Torbett B. Transcription factor PU.1 is necessary for development of thymic and myeloid progenitor-derived dendritic cells. J Immunol. 2000;164:1855-61 pubmed..Our findings indicate that PU.1 regulates the development of both thymic and myeloid progenitor-derived populations of DCs, and expand its known role in hematopoietic development. ..
- Spain L, Guerriero A, Kunjibettu S, Scott E. T cell development in PU.1-deficient mice. J Immunol. 1999;163:2681-7 pubmed..These data demonstrate that PU.1 is not absolutely required for T cell development, but does play a role in efficient commitment and/or early differentiation of most T progenitors. ..
- Krysinska H, Hoogenkamp M, Ingram R, Wilson N, Tagoh H, Laslo P, et al. A two-step, PU.1-dependent mechanism for developmentally regulated chromatin remodeling and transcription of the c-fms gene. Mol Cell Biol. 2007;27:878-87 pubmed..The two-step mechanism of developmental gene activation that we describe here may be utilized to regulate gene activity in a variety of developmental pathways. ..
- Weigelt K, Lichtinger M, Rehli M, Langmann T. Transcriptomic profiling identifies a PU.1 regulatory network in macrophages. Biochem Biophys Res Commun. 2009;380:308-12 pubmed publisher..1 target gene Ptpro was identified by exon arrays and PU.1 binding to an intronic promoter was demonstrated. In conclusion, we present a PU.1 transcriptional network with novel validated PU.1 target genes. ..
- Back J, Allman D, Chan S, Kastner P. Visualizing PU.1 activity during hematopoiesis. Exp Hematol. 2005;33:395-402 pubmed..1 expression. Our study provides a detailed visualization of PU.1 gene activity in hematopoietic cells, and shows that highly dynamic regulation of PU.1 accompanies cell fate decisions during hematopoiesis. ..
- Ahyi A, Chang H, Dent A, Nutt S, Kaplan M. IFN regulatory factor 4 regulates the expression of a subset of Th2 cytokines. J Immunol. 2009;183:1598-606 pubmed publisher..Further heterogeneity of IRF4 expression was observed in Th2 cells analyzed for expression of multiple Th2 cytokines. Thus, IRF4 promotes the expression of a subset of Th2 cytokines and contributes to Th2 heterogeneity. ..
- Nutt S, Metcalf D, D Amico A, Polli M, Wu L. Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors. J Exp Med. 2005;201:221-31 pubmed..Thus, down-regulation of PU.1 expression in the CMP is the first molecularly identified event associated with the restriction of differentiation to erythroid and megakaryocyte lineages. ..
- DeKoter R, Walsh J, Singh H. PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors. EMBO J. 1998;17:4456-68 pubmed..1 into mutant progenitors restores responsiveness to myeloid-specific cytokines and development of mature granulocytes and macrophages. Thus PU.1 controls myelopoiesis by regulating both proliferation and differentiation pathways. ..
- Iwasaki H, Somoza C, Shigematsu H, Duprez E, Iwasaki Arai J, Mizuno S, et al. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood. 2005;106:1590-600 pubmed..Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages. ..
- Pospisil V, Vargova K, Kokavec J, Rybarova J, Savvulidi F, Jonasova A, et al. Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation. EMBO J. 2011;30:4450-64 pubmed publisher..We propose that upon macrophage differentiation PU.1 represses the miR-17-92 cluster promoter by an Egr-2/Jarid1b-mediated H3K4 demethylation mechanism whose deregulation may contribute to leukaemic states. ..
- Hu R, Sharma S, Bronisz A, Srinivasan R, Sankar U, Ostrowski M. Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors. Mol Cell Biol. 2007;27:4018-27 pubmed..This work provides a mechanism to account for the modulation of MITF and PU.1 activity in committed myeloid progenitors prior to the initiation of osteoclast differentiation in response to the appropriate extracellular signals. ..
- DeKoter R, Lee H, Singh H. PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity. 2002;16:297-309 pubmed..1 in early B cell development, it is not required. These results demonstrate that PU.1 functions to regulate early B cell development in part by controlling the expression of the IL-7Ralpha gene. ..
- Chang H, Han L, Jabeen R, Carotta S, Nutt S, Kaplan M. PU.1 regulates TCR expression by modulating GATA-3 activity. J Immunol. 2009;183:4887-94 pubmed publisher..1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1(lck-/-)). Although deletion of PU...
- Chou S, Khandros E, Bailey L, Nichols K, Vakoc C, Yao Y, et al. Graded repression of PU.1/Sfpi1 gene transcription by GATA factors regulates hematopoietic cell fate. Blood. 2009;114:983-94 pubmed publisher..We used immortalized Gata1(-) erythromegakaryocytic progenitor cells to study how PU.1/Sfpi1 expression is regulated by GATA-1 and GATA-2, a related factor that is normally expressed at earlier stages of ..
- DeKoter R, Geadah M, Khoosal S, Xu L, Thillainadesan G, Torchia J, et al. Regulation of follicular B cell differentiation by the related E26 transformation-specific transcription factors PU.1, Spi-B, and Spi-C. J Immunol. 2010;185:7374-84 pubmed publisher..1 (Sfpi1) or Spi-B (Spib)...
- Moreau Gachelin F, Tavitian A, Tambourin P. Spi-1 is a putative oncogene in virally induced murine erythroleukaemias. Nature. 1988;331:277-80 pubmed..A 4.0-kilobase messenger RNA was detected in rearranged tumours. No Spi-1 rearrangement was detected in other virally induced myeloid, lymphoid or erythroid tumours tested...
- Lloberas J, Soler C, Celada A. The key role of PU.1/SPI-1 in B cells, myeloid cells and macrophages. Immunol Today. 1999;20:184-9 pubmed
- Scott E, Fisher R, Olson M, Kehrli E, Simon M, Singh H. PU.1 functions in a cell-autonomous manner to control the differentiation of multipotential lymphoid-myeloid progenitors. Immunity. 1997;6:437-47 pubmed..Finally, the Ikaros gene is expressed in PU.1 mutant embryos, suggesting that PU.1 and Ikaros are independently required for specification of embryonic lymphoid cell fates. ..
- Luchin A, Suchting S, Merson T, Rosol T, Hume D, Cassady A, et al. Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem. 2001;276:36703-10 pubmed..Taken in total, the results afford an example of how lineage-specific gene regulation can be achieved by the combinatorial action of two broadly expressed transcription factors. ..
- Schmidt M, Bies J, Tamura T, Ozato K, Wolff L. The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells. Blood. 2004;103:4142-9 pubmed
- Anderson K, Smith K, Conners K, McKercher S, Maki R, Torbett B. Myeloid development is selectively disrupted in PU.1 null mice. Blood. 1998;91:3702-10 pubmed..1 gene disruption affects a number of developmentally regulated hematopoietic processes that can, at least in part, explain the changes in myeloid development and reduction in myeloid and neutrophil expansion observed in PU.1 null mice. ..
- Parganas E, Wang D, Stravopodis D, Topham D, Marine J, Teglund S, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998;93:385-95 pubmed..Therefore, Jak2 plays a critical, nonredundant role in the function of a specific group of cytokines receptors. ..
- Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E, et al. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity. 2010;32:317-28 pubmed publisher..We suggest that this may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation. ..
- Anderson K, Smith K, Perkin H, Hermanson G, Anderson C, Jolly D, et al. PU.1 and the granulocyte- and macrophage colony-stimulating factor receptors play distinct roles in late-stage myeloid cell differentiation. Blood. 1999;94:2310-8 pubmed..These studies reinforce the idea that availability of PU.1 is crucial for normal myeloid development and clarify some of the molecular events in developing neutrophils and macrophages that are critically dependent on PU.1. ..
- Kirstetter P, Anderson K, Porse B, Jacobsen S, Nerlov C. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol. 2006;7:1048-56 pubmed..cell function was associated with decreased expression of Cdkn1a (encoding the cell cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 (encoding the transcription factors PU...
- Rosenbauer F, Owens B, Yu L, Tumang J, Steidl U, Kutok J, et al. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat Genet. 2006;38:27-37 pubmed..1 (Sfpi1) developed acute myeloid leukemia. Here we show that the URE has an essential role in orchestrating the dynamic PU...
- Stopka T, Amanatullah D, Papetti M, Skoultchi A. PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure. EMBO J. 2005;24:3712-23 pubmed
- Geng Y, Laslo P, Barton K, Wang C. Transcriptional regulation of CD1D1 by Ets family transcription factors. J Immunol. 2005;175:1022-9 pubmed..1-deficient myeloid cells. These findings are the first to demonstrate that Ets proteins are involved in the transcriptional regulation of CD1D1 and that they may function uniquely in different cell types. ..
- Klemsz M, McKercher S, Celada A, Van Beveren C, Maki R. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990;61:113-24 pubmed..1 protein placed the DNA binding domain in the highly basic carboxy-terminal domain of the protein. The amino acid sequence in the binding domain of PU.1 has considerable identity with proteins belonging to the ets oncogene family. ..
- Martin P, D Souza D, Martin J, Grose R, Cooper L, Maki R, et al. Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells. Curr Biol. 2003;13:1122-8 pubmed..We also show that hyperinnervation of the wound site, previously believed to be a consequence of inflammation, is present in the PU.1 null wound, too. ..
- Mueller B, Pabst T, Osato M, Asou N, Johansen L, Minden M, et al. Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood. 2002;100:998-1007 pubmed..1 target genes. This is the first report of mutations in the PU.1 gene in human neoplasia and suggests that disruption of PU.1 function contributes to the block in differentiation found in AML patients. ..
- Guerriero A, Langmuir P, Spain L, Scott E. PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells. Blood. 2000;95:879-85 pubmed..PU. 1(-/-)lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC. ..
- McKercher S, Torbett B, Anderson K, Henkel G, Vestal D, Baribault H, et al. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 1996;15:5647-58 pubmed..While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages. ..
- McKercher S, Henkel G, Maki R. The transcription factor PU.1 does not regulate lineage commitment but has lineage-specific effects. J Leukoc Biol. 1999;66:727-32 pubmed..Rescue of early monocytic cells by transfection with the PU.1 gene results in renewed development to macrophages. These results demonstrate that PU.1 is an important regulator in the development of cells in the hematopoietic system. ..
- Chang H, Sehra S, Goswami R, Yao W, Yu Q, Stritesky G, et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol. 2010;11:527-34 pubmed publisher..Together our data suggest a critical role for PU.1 in generating the IL-9-producing (T(H)9) phenotype and in the development of allergic inflammation. ..
- Schweitzer B, DeKoter R. Analysis of gene expression and Ig transcription in PU.1/Spi-B-deficient progenitor B cell lines. J Immunol. 2004;172:144-54 pubmed..Taken together, our observations suggest that reduction of PU.1 and/or Spi-B activity in pro-B cells promotes their differentiation to a stage intermediate between late pro-B cells and large pre-B cells. ..
- Leddin M, Perrod C, Hoogenkamp M, Ghani S, Assi S, Heinz S, et al. Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells. Blood. 2011;117:2827-38 pubmed publisher..1 regulates its expression in B cells and macrophages by differentially associating with cell type-specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. ..
- Back J, Dierich A, Bronn C, Kastner P, Chan S. PU.1 determines the self-renewal capacity of erythroid progenitor cells. Blood. 2004;103:3615-23 pubmed..These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage. ..
- Carotta S, Dakic A, D Amico A, Pang S, Greig K, Nutt S, et al. The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity. 2010;32:628-41 pubmed publisher..Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU...
- Anderson K, Smith K, Pio F, Torbett B, Maki R. Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competent. Blood. 1998;92:1576-85 pubmed..1-deficient cells. Our results indicate that PU.1 is not necessary for neutrophil lineage commitment but is essential for normal development, maturation, and function of neutrophils. ..
- Henkel G, McKercher S, Leenen P, Maki R. Commitment to the monocytic lineage occurs in the absence of the transcription factor PU.1. Blood. 1999;93:2849-58 pubmed..The combined data shows that PU.1 is absolutely required for macrophage development after commitment to this lineage. ..
- Chang H, Zhang S, Thieu V, Slee R, Bruns H, Laribee R, et al. PU.1 expression delineates heterogeneity in primary Th2 cells. Immunity. 2005;22:693-703 pubmed..Thus, the expression of PU.1 in subsets of Th2 cells establishes a defined cytokine profile and contributes towards establishing the spectrum of cytokine production observed in Th2 populations. ..
- Rimmelé P, Kosmider O, Mayeux P, Moreau Gachelin F, Guillouf C. Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation. Blood. 2007;109:3007-14 pubmed..These findings reveal 2 distinct roles for Spi-1 during erythroleukemogenesis: Spi-1 blocks the erythroid differentiation program and acts to impair apoptotic death in cooperation with an Epo signaling...
- Steidl U, Rosenbauer F, Verhaak R, Gu X, Ebralidze A, Otu H, et al. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet. 2006;38:1269-77 pubmedKnockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as 'PU...
- Scott E, Simon M, Anastasi J, Singh H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science. 1994;265:1573-7 pubmed..Thus, the developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor. ..
- Juban G, Giraud G, Guyot B, Belin S, Diaz J, Starck J, et al. Spi-1 and Fli-1 directly activate common target genes involved in ribosome biogenesis in Friend erythroleukemic cells. Mol Cell Biol. 2009;29:2852-64 pubmed publisher..These data lead us to propose that the oncogenicity of Spi-1, Fli-1, and possibly other ETS transcription factors may involve their ability to stimulate ribosome biogenesis. ..
- Cook W, McCaw B, Herring C, John D, Foote S, Nutt S, et al. PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain. Blood. 2004;104:3437-44 pubmed..1 normally suppresses development of myeloid leukemia by promoting differentiation and that the combination of gene deletion and a point mutation that impairs its ability to bind DNA is particularly leukemogenic. ..
- Carlsson R, Hjalmarsson A, Liberg D, Persson C, Leanderson T. Genomic structure of mouse SPI-C and genomic structure and expression pattern of human SPI-C. Gene. 2002;299:271-8 pubmed..Finally a phylogenetic prediction analysis of SPI-group protein sequences suggest that the SPI-C proteins form a distinct subgroup, with human SPI-C being closest related to the mouse SPI-C protein. ..
- Hegde S, Hankey P, Paulson R. Self-renewal of leukemia stem cells in Friend virus-induced erythroleukemia requires proviral insertional activation of Spi1 and hedgehog signaling but not mutation of p53. Stem Cells. 2012;30:121-30 pubmed publisher..of disease, a clonal leukemia develops through the acquisition of new mutations--proviral insertional activation of Spi1/Pu.1 and mutation of p53...
- Weber C, Telerman S, Reimer A, Sequeira I, Liakath Ali K, Arwert E, et al. Macrophage Infiltration and Alternative Activation during Wound Healing Promote MEK1-Induced Skin Carcinogenesis. Cancer Res. 2016;76:805-817 pubmed publisher..These findings highlight the importance of cancer immunotherapies aiming to polarize tumor-associated macrophages toward an antitumor phenotype. ..
- Yashiro T, Kasakura K, Oda Y, Kitamura N, Inoue A, Nakamura S, et al. The hematopoietic cell-specific transcription factor PU.1 is critical for expression of CD11c. Int Immunol. 2017;29:87-94 pubmed publisher..1. Taken together, these results indicate that PU.1 functions as a positive regulator of CD11c gene expression by directly binding to the Itgax promoter and through transactivation of the Irf4 gene. ..
- Kelly P, Dakic A, Adams J, Nutt S, Strasser A. Tumor growth need not be driven by rare cancer stem cells. Science. 2007;317:337 pubmed..We suggest that the low frequency of tumor-sustaining cells observed in xenotransplantation studies may reflect the limited ability of human tumor cells to adapt to growth in a foreign (mouse) milieu. ..
- Schweitzer B, Huang K, Kamath M, Emelyanov A, Birshtein B, DeKoter R. Spi-C has opposing effects to PU.1 on gene expression in progenitor B cells. J Immunol. 2006;177:2195-207 pubmed..Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes. ..