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The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling.
Schreiber, Lisa Pietzsch, Beate Floess, Stefan Farah, Carla Jänsch, Lothar Schmitz, Ingo Huehn, Jochen
Schreiber, Lisa
Pietzsch, Beate
Floess, Stefan
Farah, Carla
Jänsch, Lothar
Schmitz, Ingo
Huehn, Jochen
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Abstract
Regulatory T cells (Tregs) obtain immunosuppressive capacity by the upregulation of forkhead box protein 3 (Foxp3), and persistent expression of this transcription factor is required to maintain their immune regulatory function and ensure immune homeostasis. Stable Foxp3 expression is achieved through epigenetic modification of the Treg-specific demethylated region (TSDR), an evolutionarily conserved non-coding element within the Foxp3 gene locus. Here, we present molecular data suggesting that TSDR enhancer activity is restricted to T cells and cannot be induced in other immune cells such as macrophages or B cells. Since NF-κB signaling has been reported to be instrumental to induce Foxp3 expression during Treg development, we analyzed how NF-κB factors are involved in the molecular regulation of the TSDR. Unexpectedly, we neither observed transcriptional activity of a previously postulated NF-κB binding site within the TSDR nor did the entire TSDR show any transcriptional responsiveness to NF-κB activation at all. Finally, the NF-κB subunit c-Rel revealed to be dispensable for epigenetic imprinting of sustained Foxp3 expression by TSDR demethylation. In conclusion, we show that NF-κB signaling is not substantially involved in TSDR-mediated stabilization of Foxp3 expression in Tregs.
Citation
The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling. 2014, 9 (2):e88318 PLoS ONE
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Article
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en
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Series/Report no.
ISSN
1932-6203