Abstract
CD4+ regulatory T cells (Tregs) maintain immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses. The core genetic program of Tregs and their ability to suppress pathologic immune responses depends on the transcription factor Foxp3. Despite progress in understanding mechanisms of Foxp3-dependent gene activation, the molecular mechanism of Foxp3-dependent gene repression remains largely unknown. We identified Eos, a zinc-finger transcription factor of the Ikaros family, as a critical mediator of Foxp3-dependent gene silencing in Tregs. Eos interacts directly with Foxp3 and induces chromatin modifications that result in gene silencing in Tregs. Silencing of Eos in Tregs abrogates their ability to suppress immune responses and endows them with partial effector function, thus demonstrating the critical role that Eos plays in Treg programming.
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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Acetylation
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Alcohol Oxidoreductases / metabolism
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Colitis / immunology
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DNA Methylation
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DNA-Binding Proteins / metabolism
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Forkhead Transcription Factors / metabolism*
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Gene Knockdown Techniques
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Gene Silencing*
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Histones / metabolism
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Humans
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics
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Jurkat Cells
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Methylation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic
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RNA Interference
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / physiology*
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Transduction, Genetic
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Zinc Fingers
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Histones
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Interleukin-2
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Nerve Tissue Proteins
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Zfpn1a4 protein, mouse
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Alcohol Oxidoreductases
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C-terminal binding protein