Abstract
The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reveal that Ikaros proteins are capable of targeting chromatin remodeling and deacetylation complexes in vivo. We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation.
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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Adenosine Triphosphatases / metabolism
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Animals
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Autoantigens / physiology
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Carrier Proteins / physiology
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Cell Fractionation
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Chromatin / metabolism*
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DNA Helicases
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DNA-Binding Proteins / physiology*
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Drosophila Proteins*
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G1 Phase / immunology
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Histone Deacetylases / metabolism
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Ikaros Transcription Factor
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Macromolecular Substances
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Mice
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Mice, Mutant Strains
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Nuclear Proteins / metabolism
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Nucleosomes / metabolism
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S Phase / immunology
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Spleen
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T-Lymphocytes / metabolism*
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Trans-Activators / physiology
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Zinc Fingers / physiology
Substances
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Autoantigens
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Carrier Proteins
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Chromatin
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DNA-Binding Proteins
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Drosophila Proteins
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Ikzf3 protein, mouse
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Macromolecular Substances
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Mi-2 protein, Drosophila
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Nuclear Proteins
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Nucleosomes
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Trans-Activators
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Transcription Factors
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Zfpn1a1 protein, mouse
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Ikaros Transcription Factor
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Histone Deacetylases
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Adenosine Triphosphatases
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Smarca4 protein, mouse
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DNA Helicases