Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells

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Serval ID
serval:BIB_4B3FD321B301
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells
Journal
Nucleic Acids Research
Author(s)
Shi  L., Qiu  D., Zhao  G., Corthesy  B., Lees-Miller  S., Reeves  W. H., Kao  P. N.
ISSN
1362-4962 (Electronic)
Publication state
Published
Issued date
2007
Volume
35
Number
7
Pages
2302-10
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Abstract
IL-2 gene expression in activated T-cells is initiated by chromatin remodeling at the IL-2 proximal promoter and conversion of a transcriptional repressor into a potent transcriptional activator. A purine-box regulator complex was purified from activated Jurkat T-cell nuclei based on sequence-specific DNA binding to the antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target DNA sequence in the proximal IL-2 promoter. ARRE DNA-binding subunits were identified as NF90, NF45 and systemic lupus erythematosis autoantigens, Ku80 and Ku70. Monoclonal antibodies to Ku80, Ku70 and NF90 specifically inhibit constitutive and inducible ARRE DNA-binding activity in Jurkat T-cells. Ku80, Ku70 and NF90 bind specifically to the IL-2 gene promoter in vivo, as demonstrated by chromatin immunoprecipitation. Activation of Jurkat T-cells and mouse primary spleen cells induces binding of Ku80 and NF90 to the IL-2 promoter in vivo, and decreases binding of Ku70 to the IL-2 promoter in vivo, and these dynamic changes are inhibited by immunosuppressants cyclosporin A and triptolide. Dynamic changes in binding of Ku80, Ku70 and NF90 to the IL-2 proximal promoter in vivo correlate with chromatin remodeling and transcriptional initiation in activated T-cells.
Keywords
Animals Antigens, Nuclear/*metabolism Binding Sites Cells, Cultured Chromatin Immunoprecipitation Cyclosporine/pharmacology DNA-Activated Protein Kinase/metabolism DNA-Binding Proteins/*metabolism Diterpenes/pharmacology Epoxy Compounds/pharmacology Humans Immunosuppressive Agents/pharmacology Interleukin-2/*genetics Jurkat Cells Lymphocyte Activation Mice Mice, Inbred C57BL Nuclear Factor 45 Protein/metabolism Nuclear Factor 90 Proteins/*metabolism Phenanthrenes/pharmacology *Promoter Regions (Genetics) Protein Subunits/metabolism Response Elements T-Lymphocytes/*immunology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:53
Last modification date
20/08/2019 13:59
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