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DNA methylation signatures of the AIRE promoter in thymic epithelial cells, thymomas and normal tissues
Vivian Kont; Astrid Murumägi; Lars-Oliver Tykocinski; Sarah A. Kinkel; Kylie E. Webster; Kai Kisand; Liina Tserel; Maire Pihlap; Philipp Ströbel; Hamish S. Scott; et al. (Profiled Author: Bruno Kyewski)
Molecular Immunology. 2011;49(3):518-526.Abstract
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. © 2011 Elsevier Ltd.
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