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DNA methylation signatures of the AIRE promoter in thymic epithelial cells, thymomas and normal tissues

Mutations in the AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which is associated with autoimmunity towards several peripheral organs. The AIRE protein is almost exclusively expressed in medullary thymic epithelial cells (mTEC) and CpG methylation in the p...

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Hauptverfasser: Kont, Vivian (Verfasst von) , Murumägi, Astrid (Verfasst von) , Tykocinski, Lars-Oliver (Verfasst von) , Kinkel, Sarah A. (Verfasst von) , Webster, Kylie E. (Verfasst von) , Kisand, Kai (Verfasst von) , Tserel, Liina (Verfasst von) , Pihlap, Maire (Verfasst von) , Ströbel, Philipp (Verfasst von) , Scott, Hamish S. (Verfasst von) , Marx, Alexander (Verfasst von) , Kyewski, Bruno (Verfasst von) , Peterson, Pärt (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 27 October 2011
In: Molecular immunology
Year: 2011, Jahrgang: 49, Heft: 3, Pages: 518-526
ISSN:1872-9142
DOI:10.1016/j.molimm.2011.09.022
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molimm.2011.09.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0161589011007632
Volltext
Verfasserangaben:Vivian Kont, Astrid Murumägi, Lars-Oliver Tykocinski, Sarah A. Kinkel, Kylie E. Webster, Kai Kisand, Liina Tserel, Maire Pihlap, Philipp Ströbel, Hamish S. Scott, Alexander Marx, Bruno Kyewski, Pärt Peterson
Beschreibung
Zusammenfassung:Mutations in the AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which is associated with autoimmunity towards several peripheral organs. The AIRE protein is almost exclusively expressed in medullary thymic epithelial cells (mTEC) and CpG methylation in the promoter of the AIRE gene has been suggested to control its tissue-specific expression pattern. We found that in human AIRE-positive medullary and AIRE-negative cortical epithelium, the AIRE promoter is hypomethylated, whereas in thymocytes, the promoter had high level of CpG methylation. Likewise, in mouse mTECs the AIRE promoter was uniformly hypomethylated. In the same vein, the AIRE promoter was hypomethylated in AIRE-negative thymic epithelial tumors (thymomas) and in several peripheral tissues. Our data are compatible with the notion that promoter hypomethylation is necessary but not sufficient for tissue-specific regulation of the AIRE gene. In contrast, a positive correlation between AIRE expression and histone H3 lysine 4 trimethylation, an active chromatin mark, was found in the AIRE promoter in human and mouse TECs.
Beschreibung:Gesehen am 07.07.2022
Beschreibung:Online Resource
ISSN:1872-9142
DOI:10.1016/j.molimm.2011.09.022

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