Ikaros

Summary

Gene Symbol: Ikaros
Description: IKAROS family zinc finger 1
Alias: 5832432G11Rik, Ikaros, LyF-1, Zfpn1a1, Znfn1a1, hlk-1, mKIAA4227, DNA-binding protein Ikaros, ikaros family zinc finger protein 1, lymphoid transcription factor LyF-1, zinc finger protein, subfamily 1A, 1 (Ikaros)
Species: mouse
Products:     Ikaros

Top Publications

  1. Sellars M, Reina San Martin B, Kastner P, Chan S. Ikaros controls isotype selection during immunoglobulin class switch recombination. J Exp Med. 2009;206:1073-87 pubmed publisher
    ..We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other ..
  2. Gurel Z, Ronni T, Ho S, Kuchar J, Payne K, Turk C, et al. Recruitment of ikaros to pericentromeric heterochromatin is regulated by phosphorylation. J Biol Chem. 2008;283:8291-300 pubmed publisher
    b>Ikaros encodes a zinc finger protein that is involved in heritable gene silencing...
  3. Hahm K, Ernst P, Lo K, Kim G, Turck C, Smale S. The lymphoid transcription factor LyF-1 is encoded by specific, alternatively spliced mRNAs derived from the Ikaros gene. Mol Cell Biol. 1994;14:7111-23 pubmed
    ..The amino acid sequence suggests that LyF-1 is a zinc finger protein encoded by the Ikaros gene, which previously was implicated in T-cell development...
  4. Sun L, Liu A, Georgopoulos K. Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. EMBO J. 1996;15:5358-69 pubmed
    The Ikaros gene, an essential regulator of lymphocyte differentiation, encodes, by means of differential splicing, protein isoforms with a distinct number of Kruppel-type zinc fingers organized in two domains...
  5. Gómez del Arco P, Koipally J, Georgopoulos K. Ikaros SUMOylation: switching out of repression. Mol Cell Biol. 2005;25:2688-97 pubmed
    b>Ikaros plays a key role in lymphocyte development and homeostasis by both potentiating and repressing gene expression. Here we show that Ikaros interacts with components of the SUMO pathway and is SUMOylated in vivo...
  6. Souabni A, Cobaleda C, Schebesta M, Busslinger M. Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity. 2002;17:781-93 pubmed
    ..lineages, we generated a heterozygous knockin mouse carrying a Pax5 minigene under the control of the Ikaros locus...
  7. Zhang J, Jackson A, Naito T, Dose M, Seavitt J, Liu F, et al. Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis. Nat Immunol. 2011;13:86-94 pubmed publisher
    ..show that activity of the Mi-2? nucleosome-remodeling and histone-deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid lineage-determining proteins...
  8. Harker N, Naito T, Cortes M, Hostert A, Hirschberg S, Tolaini M, et al. The CD8alpha gene locus is regulated by the Ikaros family of proteins. Mol Cell. 2002;10:1403-15 pubmed
    b>Ikaros family members are important regulatory factors in lymphocyte development...
  9. Ng S, Yoshida T, Zhang J, Georgopoulos K. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity. 2009;30:493-507 pubmed publisher
    ..Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic ..

More Information

Publications63

  1. Urban J, Winandy S. Ikaros null mice display defects in T cell selection and CD4 versus CD8 lineage decisions. J Immunol. 2004;173:4470-8 pubmed
    Previous evidence suggested that the hemopoietic-specific nuclear factor Ikaros regulates TCR signaling thresholds in mature T cells...
  2. Liu Z, Widlak P, Zou Y, Xiao F, Oh M, Li S, et al. A recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus. Immunity. 2006;24:405-15 pubmed
    ..the targeting of Igkappa transgenes in pre-B and B cells to centromeric heterochromatin and associates with Ikaros, a repressor protein that also colocalizes with centromeric heterochromatin...
  3. Goldmit M, Ji Y, Skok J, Roldan E, Jung S, Cedar H, et al. Epigenetic ontogeny of the Igk locus during B cell development. Nat Immunol. 2005;6:198-203 pubmed
    ..the other allele was recruited to heterochromatin, where it was associated with heterochromatin protein-gamma and Ikaros. These events in cis made only one allele accessible to trans-acting factors, such as RelB, which mediated DNA ..
  4. Kirstetter P, Thomas M, Dierich A, Kastner P, Chan S. Ikaros is critical for B cell differentiation and function. Eur J Immunol. 2002;32:720-30 pubmed
    The Ikaros gene encodes a zinc-finger transcription factor required during early B cell development, as B-lineage cells are absent in mice lacking Ikaros...
  5. Winandy S, Wu P, Georgopoulos K. A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. Cell. 1995;83:289-99 pubmed
    The Ikaros gene is essential for lymphoid lineage specification. As previously reported, mice homozygous for a mutation in the Ikaros DNA-binding domain fail to generate mature lymphocytes as well as their earliest described progenitors...
  6. Keys J, Tallack M, Zhan Y, Papathanasiou P, Goodnow C, Gaensler K, et al. A mechanism for Ikaros regulation of human globin gene switching. Br J Haematol. 2008;141:398-406 pubmed publisher
    ..Here we show that the transcription factor Ikaros plays a major role in the formation of the beta-globin ACH, and in haemoglobin switching...
  7. Sridharan R, Smale S. Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes. J Biol Chem. 2007;282:30227-38 pubmed
    b>Ikaros is the founding member of a small family of C2H2 zinc-finger DNA-binding proteins that carry out critical functions during lymphocyte development...
  8. Thomas R, Chunder N, Chen C, Umetsu S, Winandy S, Wells A. Ikaros enforces the costimulatory requirement for IL2 gene expression and is required for anergy induction in CD4+ T lymphocytes. J Immunol. 2007;179:7305-15 pubmed
    ..The IL2 promoter contains consensus-binding elements for Ikaros, a lymphocyte-specific zinc-finger DNA-binding protein that can regulate gene expression by recruiting chromatin-..
  9. Payne K, Huang G, Sahakian E, Zhu J, Barteneva N, Barsky L, et al. Ikaros isoform x is selectively expressed in myeloid differentiation. J Immunol. 2003;170:3091-8 pubmed
    The Ikaros gene is alternately spliced to generate multiple DNA-binding and nonbinding isoforms that have been implicated as regulators of hematopoiesis, particularly in the lymphoid lineages...
  10. Ström L, Lundgren M, Severinson E. Binding of Ikaros to germline Ig heavy chain gamma1 and epsilon promoters. Mol Immunol. 2003;39:771-82 pubmed
    ..b>Ikaros is an abundant nuclear protein expressed in hematopoietic cells...
  11. Umetsu S, Winandy S. Ikaros is a regulator of Il10 expression in CD4+ T cells. J Immunol. 2009;183:5518-25 pubmed publisher
    IL-10 is a regulatory cytokine critical for controlling inflammatory responses. Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4(+) T cells...
  12. Alkhatib A, Werner M, Hug E, Herzog S, Eschbach C, Faraidun H, et al. FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination. J Exp Med. 2012;209:395-406 pubmed publisher
    ..show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-..
  13. Schjerven H, McLaughlin J, Arenzana T, Frietze S, Cheng D, Wadsworth S, et al. Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros. Nat Immunol. 2013;14:1073-83 pubmed publisher
    ..Here we found that mice lacking finger 1 or finger 4 of Ikaros exhibited distinct subsets of the hematological defects of Ikaros-null mice...
  14. Koipally J, Heller E, Seavitt J, Georgopoulos K. Unconventional potentiation of gene expression by Ikaros. J Biol Chem. 2002;277:13007-15 pubmed
    b>Ikaros is essential for the normal development and regulated proliferation of lymphoid cells...
  15. Georgopoulos K, Moore D, Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science. 1992;258:808-12 pubmed
    ..control differentiation into the T cell lineage, a complementary DNA was isolated encoding a zinc finger protein (Ikaros) related to the Drosophila gap protein Hunchback...
  16. Georgopoulos K, Winandy S, Avitahl N. The role of the Ikaros gene in lymphocyte development and homeostasis. Annu Rev Immunol. 1997;15:155-76 pubmed
    The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger proteins, is described as a central regulator of lymphocyte differentiation...
  17. Bottardi S, Ross J, Bourgoin V, Fotouhi Ardakani N, Affar E, Trudel M, et al. Ikaros and GATA-1 combinatorial effect is required for silencing of human gamma-globin genes. Mol Cell Biol. 2009;29:1526-37 pubmed publisher
    ..In this report we provide in vivo evidence that endogenous Ikaros is recruited to the human beta-globin locus and targets the histone deacetylase HDAC1 and the chromatin remodeling ..
  18. Gómez del Arco P, Maki K, Georgopoulos K. Phosphorylation controls Ikaros's ability to negatively regulate the G(1)-S transition. Mol Cell Biol. 2004;24:2797-807 pubmed
    b>Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma...
  19. QUIRION M, Gregory G, Umetsu S, Winandy S, Brown M. Cutting edge: Ikaros is a regulator of Th2 cell differentiation. J Immunol. 2009;182:741-5 pubmed
    b>Ikaros, a hematopoietic transcription factor, has well defined effects on early lymphocyte development in the bone marrow and thymus...
  20. Dumortier A, Jeannet R, Kirstetter P, Kleinmann E, Sellars M, dos Santos N, et al. Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice. Mol Cell Biol. 2006;26:209-20 pubmed
    The Ikaros transcription factor is both a key regulator of lymphocyte differentiation and a tumor suppressor in T lymphocytes. Mice carrying a hypomorphic mutation (Ik(L/L)) in the Ikaros gene all develop thymic lymphomas...
  21. Molnar A, Georgopoulos K. The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins. Mol Cell Biol. 1994;14:8292-303 pubmed
    We previously described the lymphocyte-restricted Ikaros gene encoding a zinc finger DNA-binding protein as a potential regulator of lymphocyte commitment and differentiation...
  22. Gregory G, Raju S, Winandy S, Brown M. Mast cell IL-4 expression is regulated by Ikaros and influences encephalitogenic Th1 responses in EAE. J Clin Invest. 2006;116:1327-36 pubmed
    ..GATA1/2 and Ikaros, factors with opposing roles in chromatin remodeling, acted at these sites...
  23. Ng S, Yoshida T, Georgopoulos K. Ikaros and chromatin regulation in early hematopoiesis. Curr Opin Immunol. 2007;19:116-22 pubmed
    ..the fate restriction of both the lympho-myeloid and the erythro-megakaryocyte progenitors is dependent on Ikaros and its associated chromatin regulators...
  24. Papathanasiou P, Perkins A, Cobb B, Ferrini R, Sridharan R, Hoyne G, et al. Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor. Immunity. 2003;19:131-44 pubmed
    ..Here we describe a mouse strain, Plastic, with a point mutation in a zinc finger of Ikaros that disrupts DNA binding but preserves efficient assembly of the full-length protein into higher order complexes...
  25. Reynaud D, Demarco I, Reddy K, Schjerven H, Bertolino E, Chen Z, et al. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat Immunol. 2008;9:927-36 pubmed publisher
    The transcription factor Ikaros is essential for B cell development. However, its molecular functions in B cell fate specification and commitment have remained elusive...
  26. Honma Y, Kiyosawa H, Mori T, Oguri A, Nikaido T, Kanazawa K, et al. Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system. FEBS Lett. 1999;447:76-80 pubmed
    We identified a novel member of the Ikaros gene family, which has critical roles in the development of lymphoid lineages. This gene, which we named Eos, was expressed predominantly in the developing central and peripheral nervous system...
  27. Kaufmann C, Yoshida T, Perotti E, Landhuis E, Wu P, Georgopoulos K. A complex network of regulatory elements in Ikaros and their activity during hemo-lymphopoiesis. EMBO J. 2003;22:2211-23 pubmed
    Regulated expression of Ikaros is critical for normal hemopoiesis and lymphocyte development...
  28. Popescu M, Gurel Z, Ronni T, Song C, Hung K, Payne K, et al. Ikaros stability and pericentromeric localization are regulated by protein phosphatase 1. J Biol Chem. 2009;284:13869-80 pubmed publisher
    b>Ikaros encodes a zinc finger protein that is involved in gene regulation and chromatin remodeling. The majority of Ikaros localizes at pericentromeric heterochromatin (PC-HC) where it regulates expression of target genes...
  29. Wang J, Nichogiannopoulou A, Wu L, Sun L, Sharpe A, Bigby M, et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity. 1996;5:537-49 pubmed
    Mice homozygous for an Ikaros null mutation display distinct defects in the development of fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and adult B lymphocytes and their earliest progenitors are absent...
  30. Gómez del Arco P, Kashiwagi M, Jackson A, Naito T, Zhang J, Liu F, et al. Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. Immunity. 2010;33:685-98 pubmed publisher
    Loss of the transcription factor Ikaros is correlated with Notch receptor activation in T cell acute lymphoblastic leukemia (T-ALL). However, the mechanism remains unknown...
  31. Kelley C, Ikeda T, Koipally J, Avitahl N, Wu L, Georgopoulos K, et al. Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Curr Biol. 1998;8:508-15 pubmed
    Normal hematopoietic development depends on the activity of the Ikaros transcription factor, which contains distinct zinc-finger domains that mediate DNA binding and protein dimerization...
  32. Avitahl N, Winandy S, Friedrich C, Jones B, Ge Y, Georgopoulos K. Ikaros sets thresholds for T cell activation and regulates chromosome propagation. Immunity. 1999;10:333-43 pubmed
    ..The Ikaros family of nuclear factors regulate this process by providing thresholds overcome by receptor signaling...
  33. Winandy S, Wu L, Wang J, Georgopoulos K. Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros. J Exp Med. 1999;190:1039-48 pubmed
    ..Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without ..
  34. Klug C, Morrison S, Masek M, Hahm K, Smale S, Weissman I. Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc Natl Acad Sci U S A. 1998;95:657-62 pubmed
    The generation of lymphoid cells in mice depends on the function of the Ikaros protein. Ikaros has been characterized as a lymphoid-restricted, zinc-finger transcription factor that is derived from an alternatively spliced message...
  35. Ma S, Pathak S, Mandal M, Trinh L, Clark M, Lu R. Ikaros and Aiolos inhibit pre-B-cell proliferation by directly suppressing c-Myc expression. Mol Cell Biol. 2010;30:4149-58 pubmed publisher
    ..We have shown previously that interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to suppress pre-B-cell proliferation...
  36. Tinsley K, Hong C, Luckey M, Park J, Kim G, Yoon H, et al. Ikaros is required to survive positive selection and to maintain clonal diversity during T-cell development in the thymus. Blood. 2013;122:2358-68 pubmed publisher
    The zinc-finger protein Ikaros is a key player in T-cell development and a potent tumor suppressor in thymocytes...
  37. Kathrein K, Lorenz R, Innes A, Griffiths E, Winandy S. Ikaros induces quiescence and T-cell differentiation in a leukemia cell line. Mol Cell Biol. 2005;25:1645-54 pubmed
    b>Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation...
  38. Kwon K, Hutter C, Sun Q, Bilic I, Cobaleda C, Malin S, et al. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity. 2008;28:751-62 pubmed publisher
  39. Nichogiannopoulou A, Trevisan M, Neben S, Friedrich C, Georgopoulos K. Defects in hemopoietic stem cell activity in Ikaros mutant mice. J Exp Med. 1999;190:1201-14 pubmed
    Here we provide evidence that the Ikaros family of DNA binding factors is critical for the activity of hemopoietic stem cells (HSCs) in the mouse...
  40. Lopez R, Schoetz S, DeAngelis K, O NEILL D, Bank A. Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci U S A. 2002;99:602-7 pubmed
    We have previously reported the structure of a chromatin remodeling complex (PYR complex) with Ikaros as its DNA binding subunit that is specifically present in adult murine and human hematopoietic cells...
  41. Kathrein K, Chari S, Winandy S. Ikaros directly represses the notch target gene Hes1 in a leukemia T cell line: implications for CD4 regulation. J Biol Chem. 2008;283:10476-84 pubmed publisher
    b>Ikaros and Notch1, two regulators of gene transcription, are critically important at many stages of T cell development...
  42. Naito T, Gómez del Arco P, Williams C, Georgopoulos K. Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2beta determine silencer activity and Cd4 gene expression. Immunity. 2007;27:723-34 pubmed
    ..Here, we revealed the antagonistic interplay between Ikaros and its associate the chromatin remodeler Mi-2beta during T cell development, as exemplified by the regulation of ..
  43. Bandyopadhyay S, Dure M, Paroder M, Soto Nieves N, Puga I, Macian F. Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells. Blood. 2007;109:2878-86 pubmed
    ..In response to calcium signaling, anergic T cells up-regulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination...
  44. McCarty A, Kleiger G, Eisenberg D, Smale S. Selective dimerization of a C2H2 zinc finger subfamily. Mol Cell. 2003;11:459-70 pubmed
    The C2H2 zinc finger is the most prevalent protein motif in the mammalian proteome. Two C2H2 fingers in Ikaros are dedicated to homotypic interactions between family members...
  45. Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, et al. Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation. EMBO J. 1997;16:2004-13 pubmed
    Development of the lymphoid system is dependent on the activity of zinc finger transcription factors encoded by the Ikaros gene...
  46. Thomas R, Chen C, Chunder N, Ma L, Taylor J, Pearce E, et al. Ikaros silences T-bet expression and interferon-gamma production during T helper 2 differentiation. J Biol Chem. 2010;285:2545-53 pubmed publisher
    ..that the tbx21 gene encoding the Th1 master regulator T-bet is a direct target of the transcriptional repressor Ikaros. In Th2 cells, which do not express T-bet, strong Ikaros binding could be detected at the endogenous tbx21 ..
  47. Yoshida T, Ng S, Zuniga Pflucker J, Georgopoulos K. Early hematopoietic lineage restrictions directed by Ikaros. Nat Immunol. 2006;7:382-91 pubmed
    b>Ikaros is expressed in early hematopoietic progenitors and is required for lymphoid differentiation...
  48. Georgopoulos K, Bigby M, Wang J, Molnar A, Wu P, Winandy S, et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell. 1994;79:143-56 pubmed
    The Ikaros gene encodes a family of early hematopoietic- and lymphocyte-restricted transcription factors...
  49. Kleinmann E, Geimer Le Lay A, Sellars M, Kastner P, Chan S. Ikaros represses the transcriptional response to Notch signaling in T-cell development. Mol Cell Biol. 2008;28:7465-75 pubmed publisher
    ..How these genes are repressed remains poorly understood. We report here that the Ikaros transcription factor plays a crucial role in repressing the transcriptional response to Notch signaling in T-cell ..
  50. Wu L, Nichogiannopoulou A, Shortman K, Georgopoulos K. Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity. 1997;7:483-92 pubmed
    The transcription factor Ikaros is a major determinant of lymphocyte differentiation. Mice homozygous for an Ikaros dominant-negative (DN-/-) mutation lack all cells of lymphoid origin, including T, B, and natural killer (NK) cells...
  51. Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity. 1999;10:345-55 pubmed
    The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system...
  52. Uckun F, Ma H, Zhang J, Ozer Z, Dovat S, Mao C, et al. Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros. Proc Natl Acad Sci U S A. 2012;109:18072-7 pubmed publisher
    b>Ikaros is a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis through transcriptional regulation of the earliest stages of lymphocyte ontogeny and differentiation...
  53. Okano H, Saito Y, Miyazawa T, Shinbo T, Chou D, Kosugi S, et al. Homozygous deletions and point mutations of the Ikaros gene in gamma-ray-induced mouse thymic lymphomas. Oncogene. 1999;18:6677-83 pubmed
    ..Interestingly, to this region the mouse Ikaros gene was mapped which was postulated to participate in oncogenic process from the study of Ikaros knockout mice...
  54. Chari S, Winandy S. Ikaros regulates Notch target gene expression in developing thymocytes. J Immunol. 2008;181:6265-74 pubmed
    Both Ikaros and Notch are essential for normal T cell development. Collaborative mutations causing a reduction in Ikaros activity and an increase in Notch activation promote T cell leukemogenesis...