Document Detail

FoxP3 enhances HIV-1 gene expression by modulating NFkappaB occupancy at the long terminal repeat in human T cells.
MedLine Citation:
PMID:  17416586     Owner:  NLM     Status:  MEDLINE    
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.
Derek Holmes; Geoffry Knudsen; Stephanie Mackey-Cushman; Lishan Su
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-04-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-28     Completed Date:  2007-07-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15973-80     Citation Subset:  IM    
Department of Microbiology and Immunology, the Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill 27599-7295, USA.
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MeSH Terms
Active Transport, Cell Nucleus / genetics
Cell Line
Cell Nucleus / genetics,  metabolism*,  virology
Chromatin / metabolism,  virology
Forkhead Transcription Factors / genetics,  metabolism*
Gene Expression Regulation, Viral* / genetics
HIV Long Terminal Repeat*
HIV-1 / metabolism*
Histones / metabolism
Interleukin-2 / biosynthesis
Promoter Regions, Genetic
Quantitative Trait Loci
T-Lymphocytes, Regulatory / metabolism*,  virology
Transcription Factor RelA / metabolism*
Virus Replication / genetics
Grant Support
Reg. No./Substance:
0/Chromatin; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Histones; 0/IL2 protein, human; 0/Interleukin-2; 0/Transcription Factor RelA

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