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dc.contributor.authorSchreiber, Lisa
dc.contributor.authorPietzsch, Beate
dc.contributor.authorFloess, Stefan
dc.contributor.authorFarah, Carla
dc.contributor.authorJänsch, Lothar
dc.contributor.authorSchmitz, Ingo
dc.contributor.authorHuehn, Jochen
dc.date.accessioned2014-11-04T14:44:26Zen
dc.date.available2014-11-04T14:44:26Zen
dc.date.issued2014en
dc.identifier.citationThe Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling. 2014, 9 (2):e88318 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid24505473en
dc.identifier.doi10.1371/journal.pone.0088318en
dc.identifier.urihttp://hdl.handle.net/10033/333703en
dc.description.abstractRegulatory 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.
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCell Line, Tumoren
dc.subject.meshDNA Methylationen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshGene Expression Regulationen
dc.subject.meshGenetic Locien
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshNF-kappa Ben
dc.subject.meshSignal Transductionen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleThe Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling.en
dc.typeArticleen
dc.contributor.departmentDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.en
dc.identifier.journalPloS oneen
refterms.dateFOA2018-06-13T15:33:16Z
html.description.abstractRegulatory 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.


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