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Control of Foxp3 stability through modulation of TET activity
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and fu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813667/ https://www.ncbi.nlm.nih.gov/pubmed/26903244 http://dx.doi.org/10.1084/jem.20151438 |
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author | Yue, Xiaojing Trifari, Sara Äijö, Tarmo Tsagaratou, Ageliki Pastor, William A. Zepeda-Martínez, Jorge A. Lio, Chan-Wang J. Li, Xiang Huang, Yun Vijayanand, Pandurangan Lähdesmäki, Harri Rao, Anjana |
author_facet | Yue, Xiaojing Trifari, Sara Äijö, Tarmo Tsagaratou, Ageliki Pastor, William A. Zepeda-Martínez, Jorge A. Lio, Chan-Wang J. Li, Xiang Huang, Yun Vijayanand, Pandurangan Lähdesmäki, Harri Rao, Anjana |
author_sort | Yue, Xiaojing |
collection | PubMed |
description | Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and function of regulatory T cells (T reg cells), a distinct lineage of CD4(+) T cells that prevent autoimmunity and maintain immune homeostasis. We show that during T reg cell development in the thymus, TET proteins mediate the loss of 5mC in T reg cell–specific hypomethylated regions, including CNS1 and CNS2, intronic cis-regulatory elements in the Foxp3 locus. Similar to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice. Vitamin C potentiates TET activity and acts through Tet2/Tet3 to increase the stability of Foxp3 expression in TGF-β–induced T reg cells. Our data suggest that targeting TET enzymes with small molecule activators such as vitamin C might increase induced T reg cell efficacy. |
format | Online Article Text |
id | pubmed-4813667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48136672016-09-07 Control of Foxp3 stability through modulation of TET activity Yue, Xiaojing Trifari, Sara Äijö, Tarmo Tsagaratou, Ageliki Pastor, William A. Zepeda-Martínez, Jorge A. Lio, Chan-Wang J. Li, Xiang Huang, Yun Vijayanand, Pandurangan Lähdesmäki, Harri Rao, Anjana J Exp Med Research Articles Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and function of regulatory T cells (T reg cells), a distinct lineage of CD4(+) T cells that prevent autoimmunity and maintain immune homeostasis. We show that during T reg cell development in the thymus, TET proteins mediate the loss of 5mC in T reg cell–specific hypomethylated regions, including CNS1 and CNS2, intronic cis-regulatory elements in the Foxp3 locus. Similar to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice. Vitamin C potentiates TET activity and acts through Tet2/Tet3 to increase the stability of Foxp3 expression in TGF-β–induced T reg cells. Our data suggest that targeting TET enzymes with small molecule activators such as vitamin C might increase induced T reg cell efficacy. The Rockefeller University Press 2016-03-07 /pmc/articles/PMC4813667/ /pubmed/26903244 http://dx.doi.org/10.1084/jem.20151438 Text en © 2016 Yue et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Yue, Xiaojing Trifari, Sara Äijö, Tarmo Tsagaratou, Ageliki Pastor, William A. Zepeda-Martínez, Jorge A. Lio, Chan-Wang J. Li, Xiang Huang, Yun Vijayanand, Pandurangan Lähdesmäki, Harri Rao, Anjana Control of Foxp3 stability through modulation of TET activity |
title | Control of Foxp3 stability through modulation of TET activity |
title_full | Control of Foxp3 stability through modulation of TET activity |
title_fullStr | Control of Foxp3 stability through modulation of TET activity |
title_full_unstemmed | Control of Foxp3 stability through modulation of TET activity |
title_short | Control of Foxp3 stability through modulation of TET activity |
title_sort | control of foxp3 stability through modulation of tet activity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813667/ https://www.ncbi.nlm.nih.gov/pubmed/26903244 http://dx.doi.org/10.1084/jem.20151438 |
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