Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 October 1992:
Vol. 258. no. 5083, pp. 808 - 812
DOI: 10.1126/science.1439790
Prev | Table of Contents | Next

Articles

Science, Vol 258, Issue 5083, 808-812
Copyright © 1992 by American Association for the Advancement of Science

articles

Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment

K Georgopoulos, DD Moore, and B Derfler

Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Charlestown 02114.

In a screen for transcriptional regulators that 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. The Ikaros protein binds to and activates the enhancer of a gene encoding an early T cell differentiation antigen, CD3 delta. During development, Ikaros messenger RNA was first detected in the mouse fetal liver and the embryonic thymus when hematopoietic and lymphoid progenitors initially colonize these organs; no expression was observed in the spleen or the bone marrow. The pattern of Ikaros gene expression and its ability to stimulate CD3 delta transcription support the model that Ikaros functions in the specification and maturation of the T lymphocyte.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Evolution of the Ikaros Gene Family: Implications for the Origins of Adaptive Immunity.
L. B. John, S. Yoong, and A. C. Ward (2009)
J. Immunol. 182, 4792-4799
   Abstract »    Full Text »    PDF »
Identification of different Ikaros cDNA transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method.
I. Iacobucci, A. Lonetti, D. Cilloni, F. Messa, A. Ferrari, R. Zuntini, S. Ferrari, E. Ottaviani, F. Arruga, S. Paolini, et al. (2008)
Haematologica 93, 1814-1821
   Abstract »    Full Text »    PDF »
The emerging role of the Ikaros stem cell factor in the neuroendocrine system.
S. Ezzat and S. L Asa (2008)
J. Mol. Endocrinol. 41, 45-51
   Abstract »    Full Text »    PDF »
Ikaros Modulates Cholesterol Uptake: A Link between Tumor Suppression and Differentiation.
S. Loeper, S. L. Asa, and S. Ezzat (2008)
Cancer Res. 68, 3715-3723
   Abstract »    Full Text »    PDF »
Recruitment of Ikaros to Pericentromeric Heterochromatin Is Regulated by Phosphorylation.
Z. Gurel, T. Ronni, S. Ho, J. Kuchar, K. J. Payne, C. W. Turk, and S. Dovat (2008)
J. Biol. Chem. 283, 8291-8300
   Abstract »    Full Text »    PDF »
The role of Ikaros in human erythroid differentiation.
M. Dijon, F. Bardin, A. Murati, M. Batoz, C. Chabannon, and C. Tonnelle (2008)
Blood 111, 1138-1146
   Abstract »    Full Text »    PDF »
Ikaros Enforces the Costimulatory Requirement for IL2 Gene Expression and Is Required for Anergy Induction in CD4+ T Lymphocytes.
R. M. Thomas, N. Chunder, C. Chen, S. E. Umetsu, S. Winandy, and A. D. Wells (2007)
J. Immunol. 179, 7305-7315
   Abstract »    Full Text »    PDF »
Predominant Interaction of Both Ikaros and Helios with the NuRD Complex in Immature Thymocytes.
R. Sridharan and S. T. Smale (2007)
J. Biol. Chem. 282, 30227-30238
   Abstract »    Full Text »    PDF »
Combinatorial effects of splice variants modulate function of Aiolos.
R. Caballero, F. Setien, L. Lopez-Serra, M. Boix-Chornet, M. F. Fraga, S. Ropero, D. Megias, M. Alaminos, E. M. Sanchez-Tapia, M. C. Montoya, et al. (2007)
J. Cell Sci. 120, 2619-2630
   Abstract »    Full Text »    PDF »
Conserved Functions of Ikaros in Vertebrate Lymphocyte Development: Genetic Evidence for Distinct Larval and Adult Phases of T Cell Development and Two Lineages of B Cells in Zebrafish.
M. Schorpp, M. Bialecki, D. Diekhoff, B. Walderich, J. Odenthal, H.-M. Maischein, A. G. Zapata, Tubingen 2000 Screen Consortium, Freiburg Screening Group, and T. Boehm (2006)
J. Immunol. 177, 2463-2476
   Abstract »    Full Text »    PDF »
The divergent roles of the segmentation gene hunchback.
J. Pinnell, P. S. Lindeman, S. Colavito, C. Lowe, and R. M. Savage (2006)
Integr. Comp. Biol. 46, 519-532
   Abstract »    Full Text »    PDF »
Distant HNF1 Site as a Master Control for the Human Class I Alcohol Dehydrogenase Gene Expression.
J.-S. Su, T.-F. Tsai, H.-M. Chang, K.-M. Chao, T.-S. Su, and S.-F. Tsai (2006)
J. Biol. Chem. 281, 19809-19821
   Abstract »    Full Text »    PDF »
Complete Sequence Assembly and Characterization of the C57BL/6 Mouse Ig Heavy Chain V Region.
C. M. Johnston, A. L. Wood, D. J. Bolland, and A. E. Corcoran (2006)
J. Immunol. 176, 4221-4234
   Abstract »    Full Text »    PDF »
Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.
S. Kim, Y.-J. Song, D. A. Higuchi, H. P. Kang, J. R. Pratt, L. Yang, C. M. Hong, J. Poursine-Laurent, K. Iizuka, A. R. French, et al. (2006)
Blood 107, 1024-1030
   Abstract »    Full Text »    PDF »
Ikaros is expressed in human extravillous trophoblasts and involved in their migration and invasion.
E. Yamamoto, T. Ito, A. Abe, F. Sido, K. Ino, A. Itakura, S. Mizutani, S. Dovat, S. Nomura, and F. Kikkawa (2005)
Mol. Hum. Reprod. 11, 825-831
   Abstract »    Full Text »    PDF »
Transgenic Expression of Helios in B Lineage Cells Alters B Cell Properties and Promotes Lymphomagenesis.
S. Dovat, E. Montecino-Rodriguez, V. Schuman, M. A. Teitell, K. Dorshkind, and S. T. Smale (2005)
J. Immunol. 175, 3508-3515
   Abstract »    Full Text »    PDF »
The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons.
L. Lei, F. Laub, M. Lush, M. Romero, J. Zhou, B. Luikart, L. Klesse, F. Ramirez, and L. F. Parada (2005)
Genes & Dev. 19, 1354-1364
   Abstract »    Full Text »    PDF »
Ikaros SUMOylation: Switching Out of Repression.
P. Gomez-del Arco, J. Koipally, and K. Georgopoulos (2005)
Mol. Cell. Biol. 25, 2688-2697
   Abstract »    Full Text »    PDF »
Thymic Anlage Is Colonized by Progenitors Restricted to T, NK, and Dendritic Cell Lineages.
K. Masuda, M. Itoi, T. Amagai, N. Minato, Y. Katsura, and H. Kawamoto (2005)
J. Immunol. 174, 2525-2532
   Abstract »    Full Text »    PDF »
Tissue Distribution of Placental Leucine Aminopeptidase/Oxytocinase During Mouse Pregnancy.
H. Kobayashi, S. Nomura, T. Mitsui, T. Ito, N. Kuno, Y. Ohno, K. Kadomatsu, T. Muramatsu, T. Nagasaka, and S. Mizutani (2004)
J. Histochem. Cytochem. 52, 113-122
   Abstract »    Full Text »    PDF »
The C-terminal Domain of Eos Forms a High Order Complex in Solution.
B. J. Westman, J. Perdomo, M. Sunde, M. Crossley, and J. P. Mackay (2003)
J. Biol. Chem. 278, 42419-42426
   Abstract »    Full Text »    PDF »
Ikaros Isoform X Is Selectively Expressed in Myeloid Differentiation.
K. J. Payne, G. Huang, E. Sahakian, J. Y. Zhu, N. S. Barteneva, L. W. Barsky, M. A. Payne, and G. M. Crooks (2003)
J. Immunol. 170, 3091-3098
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Mouse delta -Opioid Receptor Gene. IKAROS-2 AND UPSTREAM STIMULATORY FACTOR SYNERGIZE IN TRANS-ACTIVATING MOUSE delta -OPIOID RECEPTOR GENE IN T CELLS.
P. Sun and H. H. Loh (2003)
J. Biol. Chem. 278, 2304-2308
   Abstract »    Full Text »    PDF »
Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX.
A. M. Krackhardt, M. Witzens, S. Harig, F. S. Hodi, A. J. Zauls, M. Chessia, P. Barrett, and J. G. Gribben (2002)
Blood 100, 2123-2131
   Abstract »    Full Text »    PDF »
A Molecular Dissection of the Repression Circuitry of Ikaros.
J. Koipally and K. Georgopoulos (2002)
J. Biol. Chem. 277, 27697-27705
   Abstract »    Full Text »    PDF »
Ikaros-CtIP Interactions Do Not Require C-terminal Binding Protein and Participate in a Deacetylase-independent Mode of Repression.
J. Koipally and K. Georgopoulos (2002)
J. Biol. Chem. 277, 23143-23149
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor 4 Is a Target for the Zinc-Finger Transcription Factor Ikaros in the Pituitary.
S. Yu, S. L. Asa, and S. Ezzat (2002)
Mol. Endocrinol. 16, 1069-1078
   Abstract »    Full Text »    PDF »
Point Mutations and Deletions in the Znfn1a1/Ikaros Gene in Chemically Induced Murine Lymphomas.
A. Karlsson, P. Soderkvist, and S.-M. Zhuang (2002)
Cancer Res. 62, 2650-2653
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Mouse delta -Opioid Receptor Gene. ROLE OF IKAROS IN THE STIMULATED TRANSCRIPTION OF MOUSE delta -OPIOID RECEPTOR GENE IN ACTIVATED T CELLS.
P. Sun and H. H. Loh (2002)
J. Biol. Chem. 277, 12854-12860
   Abstract »    Full Text »    PDF »
Unconventional Potentiation of Gene Expression by Ikaros.
J. Koipally, E. J. Heller, J. R. Seavitt, and K. Georgopoulos (2002)
J. Biol. Chem. 277, 13007-13015
   Abstract »    Full Text »    PDF »
High frequency of Ikaros isoform 6 expression in acute myelomonocytic and monocytic leukemias: implications for up-regulation of the antiapoptotic protein Bcl-XL in leukemogenesis.
T. Yagi, S. Hibi, M. Takanashi, G. Kano, Y. Tabata, T. Imamura, T. Inaba, A. Morimoto, S. Todo, and S. Imashuku (2002)
Blood 99, 1350-1355
   Abstract »    Full Text »    PDF »
Non-cell autonomous requirement for the bloodless gene in primitive hematopoiesis of zebrafish.
E. C. Liao, N. S. Trede, D. Ransom, A. Zapata, M. Kieran, and L. I. Zon (2002)
Development 129, 649-659
   Abstract »    Full Text »    PDF »
Ikaros, a Lymphoid-Cell-Specific Transcription Factor, Contributes to the Leukemogenic Phenotype of a Mink Cell Focus-Inducing Murine Leukemia Virus.
N. L. DiFronzo, C. T. Leung, M. K. Mammel, K. Georgopoulos, B. J. Taylor, and Q. N. Pham (2002)
J. Virol. 76, 78-87
   Abstract »    Full Text »    PDF »
Forced expression of the Ikaros 6 isoform in human placental blood CD34+ cells impairs their ability to differentiate toward the B-lymphoid lineage.
C. Tonnelle, F. Bardin, C. Maroc, A.-M. Imbert, F. Campa, A. Dalloul, C. Schmitt, and C. Chabannon (2001)
Blood 98, 2673-2680
   Abstract »    Full Text »    PDF »
Grasshopper hunchback expression reveals conserved and novel aspects of axis formation and segmentation.
N. H. Patel, D. C. Hayward, S. Lall, N. R. Pirkl, D. DiPietro, and E. E. Ball (2001)
Development 128, 3459-3472
   Abstract »    Full Text »    PDF »
Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage.
M. Itoi, H. Kawamoto, Y. Katsura, and T. Amagai (2001)
Int. Immunol. 13, 1203-1211
   Abstract »    Full Text »    PDF »
Cutting Edge: Predominant Expression of a Novel Ikaros Isoform in Normal Human Hemopoiesis.
K. J. Payne, J.-H. Nicolas, J. Y. Zhu, L. W. Barsky, and G. M. Crooks (2001)
J. Immunol. 167, 1867-1870
   Abstract »    Full Text »    PDF »
Evolution and Characterization of Tetraonine Endogenous Retrovirus: a New Virus Related to Avian Sarcoma and Leukosis Viruses.
D. E. Dimcheff, M. Krishnan, and D. P. Mindell (2001)
J. Virol. 75, 2002-2009
   Abstract »    Full Text »
mKlf7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons.
L Lei, L Ma, S Nef, T Thai, and L. Parada (2001)
Development 128, 1147-1158
   Abstract »    PDF »
An Ikaros-Containing Chromatin-Remodeling Complex in Adult-Type Erythroid Cells.
D. W. O'Neill, S. S. Schoetz, R. A. Lopez, M. Castle, L. Rabinowitz, E. Shor, D. Krawchuk, M. G. Goll, M. Renz, H.-P. Seelig, et al. (2000)
Mol. Cell. Biol. 20, 7572-7582
   Abstract »    Full Text »
Overlapping Expression of Early B-Cell Factor and Basic Helix-Loop-Helix Proteins as a Mechanism To Dictate B-Lineage-Specific Activity of the lambda 5 Promoter.
M. Sigvardsson (2000)
Mol. Cell. Biol. 20, 3640-3654
   Abstract »    Full Text »
The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma.
Y. Hosokawa, Y. Maeda, R. Ichinohasama, I. Miura, M. Taniwaki, and M. Seto (2000)
Blood 95, 2719-2721
   Abstract »    Full Text »    PDF »
Murine Pro-B Cells Require IL-7 and Its Receptor Complex to Up-Regulate IL-7R{alpha}, Terminal Deoxynucleotidyltransferase, and c{micro} Expression.
C. Wei, R. Zeff, and I. Goldschneider (2000)
J. Immunol. 164, 1961-1970
   Abstract »    Full Text »    PDF »
PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells.
A. Guerriero, P. B. Langmuir, L. M. Spain, and E. W. Scott (2000)
Blood 95, 879-885
   Abstract »    Full Text »    PDF »
Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression.
L Ma, J Merenmies, and L. Parada (2000)
Development 127, 3777-3788
   Abstract »    PDF »
Expression of Aberrantly Spliced Oncogenic Ikaros Isoforms in Childhood Acute Lymphoblastic Leukemia.
L. Sun, P. A. Goodman, C. M. Wood, M.-L. Crotty, M. Sensel, H. Sather, C. Navara, J. Nachman, P. G. Steinherz, P. S. Gaynon, et al. (1999)
J. Clin. Oncol. 17, 3753-3766
   Abstract »    Full Text »    PDF »
Pre-T Cell Receptor (Tcr) and Tcr-Controlled Checkpoints in T Cell Differentiation Are Set by Ikaros.
S. Winandy, L. Wu, J.-H. Wang, and K. Georgopoulos (1999)
J. Exp. Med. 190, 1039-1048
   Abstract »    Full Text »    PDF »
Neurogenetics of the Cerebellar System.
K. J. Millen, J. H. Millonig, R. J. T. Wingate, J. Alder, and M. E. Hatten (1999)
J Child Neurol 14, 574-581
   Abstract »    PDF »
Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia.
L. Sun, N. Heerema, L. Crotty, X. Wu, C. Navara, A. Vassilev, M. Sensel, G. H. Reaman, and F. M. Uckun (1999)
PNAS 96, 680-685
   Abstract »    Full Text »    PDF »
Ikaros Chromatin Remodeling Complexes in the Control of Differentiation of the Hemo-lymphoid System.
J. KOIPALLY, J. KIM, B. JONES, A. JACKSON, N. AVITAHL, S. WINANDY, M. TREVISAN, A. NICHOGIANNOPOULOU, C. KELLEY, and K. GEORGOPOULOS (1999)
Cold Spring Harb Symp Quant Biol 64, 79-86
   Abstract »    PDF »
Mechanisms of Transcriptional Regulation in Lymphocyte Progenitors: Insight from an Analysis of the Terminal Transferase Promoter.
P. ERNST, K. HAHM, B. S. COBB, K. E. BROWN, L.A. TRINH, A.S. MCCARTY, M. MERKENSCHLAGER, C.A. KLUG, A.G. FISHER, and S.T. SMALE (1999)
Cold Spring Harb Symp Quant Biol 64, 87-98
   Abstract »    PDF »
Characterization of prethymic progenitors within the chicken embryo.
M. Lampisuo, J. Liippo, O. Vainio, K. M. McNagny, J. Kulmala, and O. Lassila (1999)
Int. Immunol. 11, 63-69
   Abstract »    Full Text »    PDF »
Down-regulation of Human Granzyme B Expression by Glucocorticoids. DEXAMETHASONE INHIBITS BINDING TO THE Ikaros AND AP-1 REGULATORY ELEMENTS OF THE GRANZYME B PROMOTER.
A. Wargnier, C. Lafaurie, S. Legros-Maida, J.-F. Bourge, F. Sigaux, M. Sasportes, and P. Paul (1998)
J. Biol. Chem. 273, 35326-35331
   Abstract »    Full Text »    PDF »
Differentiation-Specific, Octamer-Dependent Costimulation of {kappa} Transcription.
D. Liberg, M. Sigvardsson, M. Bemark, and T. Leanderson (1998)
J. Immunol. 160, 3899-3907
   Abstract »    Full Text »    PDF »
Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin.
K. Hahm, B. S. Cobb, A. S. McCarty, K. E. Brown, C. A. Klug, R. Lee, K. Akashi, I. L. Weissman, A. G. Fisher, and S. T. Smale (1998)
Genes & Dev. 12, 782-796
   Abstract »    Full Text »
FLT-3 Ligand and Marrow Stroma-Derived Factors Promote CD3gamma , CD3delta , CD3zeta , and RAG-2 Gene Expression in Primary Human CD34+LIN-DR- Marrow Progenitors.
P. M. Gaffney, J. Lund, and J. S. Miller (1998)
Blood 91, 1662-1670
   Abstract »    Full Text »    PDF »
Biology and Treatment of Childhood T-Lineage Acute Lymphoblastic Leukemia.
F. M. Uckun, M. G. Sensel, L. Sun, P. G. Steinherz, M. E. Trigg, N. A. Heerema, H. N. Sather, G. H. Reaman, and P. S. Gaynon (1998)
Blood 91, 735-746
   Full Text »    PDF »
Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes.
C. A. Klug, S. J. Morrison, M. Masek, K. Hahm, S. T. Smale, and I. L. Weissman (1998)
PNAS 95, 657-662
   Abstract »    Full Text »    PDF »
Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog.
J. Kohtz, D. Baker, G Corte, and G Fishell (1998)
Development 125, 5079-5089
   Abstract »    PDF »
Robust, But Transient Expression of Adeno-Associated Virus-Transduced Genes During Human T Lymphopoiesis.
J. P. Gardner, H. Zhu, P. C. Colosi, G. J. Kurtzman, and D. T. Scadden (1997)
Blood 90, 4854-4864
   Abstract »    Full Text »    PDF »
Mutational Analysis of the Murine Granzyme B Gene Promoter in Primary T Cells and a T Cell Clone.
C. K. Babichuk and R. C. Bleackley (1997)
J. Biol. Chem. 272, 18564-18571
   Abstract »    Full Text »    PDF »
Receptor Protein Tyrosine Phosphatase Gamma, Ptpgamma , Regulates Hematopoietic Differentiation.
C. Sorio, P. Melotti, D. D'Arcangelo, J. Mendrola, B. Calabretta, C. M. Croce, and K. Huebner (1997)
Blood 90, 49-57
   Abstract »    Full Text »    PDF »
The hardwiring of development: organization and function of genomic regulatory systems.
M. Arnone and E. Davidson (1997)
Development 124, 1851-1864
   Abstract »    PDF »
In Vivo Regulation of Murine Granzyme B Gene Transcription in Activated Primary T Cells.
C. K. Babichuk, B. L. Duggan, and R. C. Bleackley (1996)
J. Biol. Chem. 271, 16485-16493
   Abstract »    Full Text »    PDF »
Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49.
X. Yang, R Zhong, and N Heintz (1996)
Development 122, 555-566
   Abstract »    PDF »
Transcription Factors and Hematopoietic Development.
S. H. Orkin and S. H. Orkin (1995)
J. Biol. Chem. 270, 4955-4958
   Full Text »    PDF »
Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities.
J. Perdomo, M. Holmes, B. Chong, and M. Crossley (2000)
J. Biol. Chem. 275, 38347-38354
   Abstract »    Full Text »    PDF »
An Intronic Ikaros-binding Element Mediates Retinoic Acid Suppression of the Kappa Opioid Receptor Gene, Accompanied by Histone Deacetylation on the Promoters.
X. Hu, J. Bi, H. H. Loh, and L.-N. Wei (2001)
J. Biol. Chem. 276, 4597-4603
   Abstract »    Full Text »    PDF »
Identification and Characterization of a Transcriptional Regulator for the lck Proximal Promoter.
A. Yamada, S. Takaki, F. Hayashi, K. Georgopoulos, R. M. Perlmutter, and K. Takatsu (2001)
J. Biol. Chem. 276, 18082-18089
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)