Eos Mediates Foxp3-Dependent Gene Silencing in CD4+ Regulatory T Cells

Immunology and Hematopoiesis Division, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Science (Impact Factor: 33.61). 09/2009; 325(5944):1142-6. DOI: 10.1126/science.1176077
Source: PubMed


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.

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Available from: Michael C Ostrowski, Oct 03, 2015
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    • "IKZF4 gene. SNPs at 12q13.2 region containing IKZF4 gene associated with diabetes mellitus type 1 and alopecia areata encoding the transcriptional factor for T cell activation [101–103]. "
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    • "The suppression of CD4+ T cells proliferation is also maintained through the interaction of Foxp3 N-terminal domain with Eos, a zinc-finger transcription factor of the Ikaros family (45). Foxp3, Eos, and the C-terminal binding protein-1 (CtBP1), form an inhibitory complex that suppresses the expression of genes. "
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    • "The repressor domain functions via a direct interaction with the transcriptional corepressor histone deacetylase-7 (HDAC7) that causes hypoacetylation of histones in the associated chromatin (Li et al., 2007). Eos, a zinc-finger transcription factor, is similarly a critical mediator of FoxP3-dependent gene silencing in Treg cells (Pan et al., 2009). Interestingly, in FoxP3-expressing cells, a greater number of FoxP3 transcriptional targets are upregulated than downregulated. "
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