Regulation of DNA Demethylation during Maturation of CD4+ Naive T Cells by the Conserved Noncoding Sequence 1
| Autor: | Kazuhisa Aoki, Osamu Kaminuma, Noriko Sato, Shoichiro Miyatake, Atsumi Yamaguchi, Takumi Hosozawa |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
RNA Untranslated Time Factors Transcription Genetic Immunology Cytokine Expression Profile Thymus Gland Biology Conserved sequence Histones Mice Gene expression Animals Immunology and Allergy Epigenetics Gene Cells Cultured Conserved Sequence Demethylation Mice Inbred BALB C Cell Differentiation DNA Methylation Molecular biology Immunity Innate DNA demethylation DNA methylation Cytokines Gene Deletion |
| Zdroj: | The Journal of Immunology. 182:7698-7707 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0801643 |
| Popis: | Demethylation of transcriptional regulatory elements and gene coding regions is an important step in the epigenetic regulation of gene expression. Several noncoding conserved regions are required for the efficient transcription of cytokine genes. In this paper, we show that the deletion of one such sequence, conserved noncoding sequence 1 (CNS-1), interferes with the efficient demethylation of Th2 cytokine genes but has little effect on histone modifications in the area. Th2 cells derived from CD4 single-positive (SP) mature thymocytes exhibit more rapid demethylation of CNS-1 and Th2-specific cytokine genes and produce more Th2 cytokines than do Th2 cells derived from CD4-positive peripheral naive T cells. De-repression of the Th1 cytokine IFN-γ was also detected in Th2-primed CD4 SP thymocytes but not in naive T cells. Our results indicate that susceptibility to demethylation determines the efficiency and kinetics of cytokine gene transcription. The extrathymic maturation step undergone by naive T cells suppresses robust and rapid cytokine expression, whereas mature CD4 SP thymocytes maintain a rapid and less-specific cytokine expression profile. Finally, we detected the methyl cytosine binding protein MBD2 at CNS-1 in mature thymocytes, suggesting that this protein may regulate the demethylation of this region. |
| Databáze: | OpenAIRE |
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