期刊
EMBO JOURNAL
卷 25, 期 11, 页码 2443-2452出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7601148
关键词
factor binding; IFN-gamma promoter; methylation T helper cells; transcription
资金
- NIAID NIH HHS [AI40416, AI50631, R01 AI050631] Funding Source: Medline
Polarization of naive CD4T cells into T helper type 2 (T(H)2) cells is characterized by expression of IL-4 and silencing of IFN-gamma. Here we show that during TH2 polarization, the DNA methyltransferase Dnmt3a is recruited to the IFN-gamma promoter and correspondingly the promoter undergoes progressive de novo methylation. Notably, the CpG located at the -53 position becomes methylated rapidly and this methylation inhibits ATF2/c-Jun and CREB transcription factor binding in vitro. In vivo, the same factors bind to the unmethylated IFN-gamma promoter in T helper type 1 (T(H)1) cells but not the methylated IFN-gamma promoter in TH2 cells. Furthermore, methylation at the -53 CpG alone is sufficient to inhibit the IFN-gamma promoter-driven reporter gene expression in a TH1 cell line. These findings suggest that rapid methylation of the evolutionarily conserved -53 CpG by Dnmt3a may suppress IFN-gamma transcription in developing TH2 cells by directly inhibiting transcription factor binding.
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