FoxP3 Enhances HIV-1 Gene Expression by Modulating NFκB Occupancy at the Long Terminal Repeat in Human T Cells
| Autor: | Derek A. Holmes, Lishan Su, Stephanie L. Mackey-Cushman, Geoffry Knudsen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Gene Expression Regulation
Viral Quantitative Trait Loci Active Transport Cell Nucleus chemical and pharmacologic phenomena Biology Virus Replication T-Lymphocytes Regulatory Biochemistry Article Cell Line Histones Gene expression Humans IL-2 receptor Promoter Regions Genetic Molecular Biology HIV Long Terminal Repeat Cell Nucleus Regulation of gene expression HEK 293 cells Transcription Factor RelA FOXP3 Acetylation Forkhead Transcription Factors hemic and immune systems Cell Biology Molecular biology Chromatin Long terminal repeat Mutation HIV-1 Interleukin-2 |
| Zdroj: | Journal of Biological Chemistry. 282:15973-15980 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m702051200 |
| Popis: | FoxP3 determines the development of CD4+CD25+ regulatory T (Treg) cells and represses interleukin-2 (IL-2) expression in Treg cells. However, human immunodeficiency virus type 1 (HIV-1) infects and replicates efficiently in FoxP3+ Treg cells. We report that, while inhibiting IL-2 gene expression, FoxP3 enhances gene expression from HIV-1 long terminal repeat (LTR). This FoxP3 activity requires both the N- and C-terminal domains and is inactivated by human IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) mutations. FoxP3 enhances HIV-1 LTR via its specific NFkappaB binding sequences in an NFkappaB-dependent fashion in T cells but not in HEK293 cells. FoxP3 decreases level of histone acetylation at the interleukin-2 locus but not at the HIV-1 LTR. Although NFkappaB nuclear translocation is not altered, FoxP3 enhances NFkappaB-p65 binding to HIV-1 LTR. These data suggest that FoxP3 modulates gene expression in a promoter sequence-dependent fashion by modulating chromatin structure and NFkappaB activity. HIV-1 LTR has evolved to both highjack the T-cell activation pathway for expression and to resist FoxP3-mediated suppression of T-cell activation. |
| Databáze: | OpenAIRE |
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