DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells

Guoying Wu, Keiji Hirabayashi, Shinya Sato, Nobuko Akiyama, Taishin Akiyama, Kunio Shiota, Shintaro Yagi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Medullary 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.Results: We identified the T-DMRs of mTECs (mTEC-T-DMRs) via genome-wide DNA methylation analysis of Aire-/- mTECs by comparison with the liver, brain, thymus, and embryonic stem cells. The hypomethylated mTEC-T-DMRs in Aire-/- mTECs were associated with mTEC-specific genes, including Aire, CD80, and Trp63, as well as other genes involved in the RANK signaling pathway. While these mTEC-T-DMRs were also hypomethylated in Aire+/+ 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 for Aire+/+ and Aire-/- mTECs but distinct from that of athymic cells and tissues.Conclusions: These 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.

Original languageEnglish
Article number58
JournalBMC Immunology
Volume13
DOIs
Publication statusPublished - 2012 Nov 2
Externally publishedYes

Fingerprint

DNA Methylation
Epithelial Cells
Epithelium
Thymus Gland
Central Tolerance
Genome
Antigens
Autoantigens
Cell Lineage
Embryonic Stem Cells
Stromal Cells

Keywords

  • Aire
  • Medullary thymic epithelial cells
  • T-DMR

ASJC Scopus subject areas

  • Immunology

Cite this

Wu, G., Hirabayashi, K., Sato, S., Akiyama, N., Akiyama, T., Shiota, K., & Yagi, S. (2012). DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells. BMC Immunology, 13, [58]. https://doi.org/10.1186/1471-2172-13-58

DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells. / Wu, Guoying; Hirabayashi, Keiji; Sato, Shinya; Akiyama, Nobuko; Akiyama, Taishin; Shiota, Kunio; Yagi, Shintaro.

In: BMC Immunology, Vol. 13, 58, 02.11.2012.

Research output: Contribution to journalArticle

Wu, G, Hirabayashi, K, Sato, S, Akiyama, N, Akiyama, T, Shiota, K & Yagi, S 2012, 'DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells', BMC Immunology, vol. 13, 58. https://doi.org/10.1186/1471-2172-13-58
Wu G, Hirabayashi K, Sato S, Akiyama N, Akiyama T, Shiota K et al. DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells. BMC Immunology. 2012 Nov 2;13. 58. https://doi.org/10.1186/1471-2172-13-58
Wu, Guoying ; Hirabayashi, Keiji ; Sato, Shinya ; Akiyama, Nobuko ; Akiyama, Taishin ; Shiota, Kunio ; Yagi, Shintaro. / DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells. In: BMC Immunology. 2012 ; Vol. 13.
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