Abstract
Ikaros proteins are required for normal T, B, and NK cell development and are postulated to activate lymphocyte-specific gene expression. Here we examined Ikaros distribution in the nucleus of B lymphocytes using confocal microscopy and a novel immunofluorescence in situ hybridization (immuno-FISH) approach. Unexpectedly, Ikaros localized to discrete heterochromatin-containing foci in interphase nuclei, which comprise clusters of centromeric DNA as defined by gamma-satellite sequences and the abundance of heterochromatin protein-1 (HP-1). Using locus-specific probes for CD2, CD4, CD8alpha, CD19, CD45, and lambda5 genes, we show that transcriptionally inactive but not transcriptionally active genes associate with Ikaros-heterochromatin foci. These findings support a model of organization of the nucleus in which repressed genes are selectively recruited into centromeric domains.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / biosynthesis
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Antigens, Differentiation, B-Lymphocyte / biosynthesis
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Antigens, Differentiation, B-Lymphocyte / genetics
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B-Lymphocytes / physiology
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Cell Line
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Cell Nucleus / physiology
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Cell Nucleus / ultrastructure
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Centromere / physiology*
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Centromere / ultrastructure
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DNA-Binding Proteins*
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Gene Expression Regulation
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Heterochromatin / physiology*
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Heterochromatin / ultrastructure
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Ikaros Transcription Factor
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Lymphoma
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Mice
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Mice, Transgenic
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Models, Genetic
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Polymerase Chain Reaction
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin-7
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Transcription Factors / analysis
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Transcription Factors / metabolism*
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Transcription, Genetic*
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Zinc Fingers
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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DNA-Binding Proteins
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Heterochromatin
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Receptors, Interleukin
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Receptors, Interleukin-7
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Transcription Factors
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Zfpn1a1 protein, mouse
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Ikaros Transcription Factor