Abstract
Ikaros and Notch1, two regulators of gene transcription, are critically important at many stages of T cell development. Deregulation of Ikaros and Notch activities cooperate to promote T cell leukemogenesis, providing evidence that they function in converging pathways in developing T cells. In this report, a mechanism for Ikaros:Notch cooperativity is described, revealing a non-redundant role for Ikaros in regulating expression of the Notch target gene Hes1 in a leukemia T cell line. We provide evidence that Ikaros directly represses Hes1 in concert with the transcriptional repressor, RBP-Jkappa, allowing for cross-talk between Notch and Ikaros that impacts regulation of CD4 expression. Taken together, these data describe a potential mechanism for Ikaros' function during T cell development and define Ikaros as an obligate repressor of Hes1.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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CD4 Antigens / biosynthesis*
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Cell Line, Tumor
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Gene Expression Regulation*
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Gene Silencing
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Homeodomain Proteins / metabolism*
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Humans
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Ikaros Transcription Factor / metabolism*
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
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Mice
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Models, Biological
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Molecular Sequence Data
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Promoter Regions, Genetic
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Receptor, Notch1 / metabolism*
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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CD4 Antigens
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Hes1 protein, mouse
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Homeodomain Proteins
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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Notch1 protein, mouse
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Receptor, Notch1
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Transcription Factor HES-1
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Zfpn1a1 protein, mouse
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Ikaros Transcription Factor