DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells
Copyright policy )DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells
AbstractBackgroundMedullary thymic epithelial cells (mTECs) are characterized by ectopic expression of self-antigens during the establishment of central tolerance. The autoimmune regulator (Aire), which is specifically expressed in mTECs, is responsible for the expression of a large repertoire of tissue-restricted antigens (TRAs) and plays a role in the development of mTECs. However, Aire-deficient mTECs still express TRAs. Moreover, a subset of mTECs, which are considered to be at a stage of terminal differentiation, exists in the Aire-deficient thymus. The phenotype of a specific cell type in a multicellular organism is governed by the epigenetic regulation system. DNA methylation modification is an important component of this system. Every cell or tissue type displays a DNA methylation profile, consisting of tissue-dependent and differentially methylated regions (T-DMRs), and this profile is involved in cell-type-specific genome usage. The aim of this study was to examine the DNA methylation profile of mTECs by using Aire-deficient mTECs as a model.ResultsWe identified the T-DMRs of mTECs (mTEC-T-DMRs) via genome-wide DNA methylation analysis ofAire−/−mTECs by comparison with the liver, brain, thymus, and embryonic stem cells. The hypomethylated mTEC-T-DMRs inAire−/−mTECs were associated with mTEC-specific genes, includingAire,CD80, andTrp63, as well as other genes involved in the RANK signaling pathway. While these mTEC-T-DMRs were also hypomethylated inAire+/+mTECs, they were hypermethylated in control thymic stromal cells. We compared the pattern of DNA methylation levels at a total of 55 mTEC-T-DMRs and adjacent regions and found that the DNA methylation status was similar forAire+/+andAire−/−mTECs but distinct from that of athymic cells and tissues.ConclusionsThese results indicate a unique DNA methylation profile that is independent of Aire in mTECs. This profile is distinct from other cell types in the thymic microenvironment and is indicated to be involved in the differentiation of the mTEC lineage.
- University of Tokyo Japan
Immunology, Medullary thymic epithelial cells, Cell Separation, Thymus Gland, Mice, Animals, Oligonucleotide Array Sequence Analysis, T-DMR, Gene Expression Profiling, AIRE Protein, Epithelial Cells, RC581-607, DNA Methylation, Mice, Inbred C57BL, Gene Expression Regulation, Organ Specificity, Aire, Leukocyte Common Antigens, Immunologic diseases. Allergy, Stromal Cells, Transcription Initiation Site, Biomarkers, Research Article, Transcription Factors
Immunology, Medullary thymic epithelial cells, Cell Separation, Thymus Gland, Mice, Animals, Oligonucleotide Array Sequence Analysis, T-DMR, Gene Expression Profiling, AIRE Protein, Epithelial Cells, RC581-607, DNA Methylation, Mice, Inbred C57BL, Gene Expression Regulation, Organ Specificity, Aire, Leukocyte Common Antigens, Immunologic diseases. Allergy, Stromal Cells, Transcription Initiation Site, Biomarkers, Research Article, Transcription Factors
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