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 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.
Molecular Pathology Group, Tartu University, 50411 Tartu, Estonia.
Vivian
V
Kont
Astrid
A
Murumägi
Lars-Oliver
LO
Tykocinski
Sarah A
SA
Kinkel
Kylie E
KE
Webster
Kai
K
Kisand
Liina
L
Tserel
Maire
M
Pihlap
Philipp
P
Ströbel
Hamish S
HS
Scott
Alexander
A
Marx
Bruno
B
Kyewski
Pärt
P
Peterson
D000818:Animals; D019175:DNA Methylation; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013945:Thymoma / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein