factor binding;
IFN-gamma promoter;
methylation T helper cells;
transcription;
D O I:
10.1038/sj.emboj.7601148
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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.
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Fujimoto, M
Kitazawa, R
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Kitazawa, R
Maeda, S
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Maeda, S
Kitazawa, S
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Grogan, JL
Mohrs, M
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Mohrs, M
Harmon, B
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Harmon, B
Lacy, DA
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Lacy, DA
Sedat, JW
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Sedat, JW
Locksley, RM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Fujimoto, M
Kitazawa, R
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Kitazawa, R
Maeda, S
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
Maeda, S
Kitazawa, S
论文数: 0引用数: 0
h-index: 0
机构:
Kobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Div Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Grogan, JL
Mohrs, M
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Mohrs, M
Harmon, B
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Harmon, B
Lacy, DA
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Lacy, DA
Sedat, JW
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
Sedat, JW
Locksley, RM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA