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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Shi L,Qiu D,Zhao G,Corthesy B,Lees-Miller S,Reeves WH,Kao PN

doi

10.1093/nar/gkm117

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

2302-10

issue

7

eissn

0305-1048

issn

1362-4962

pii

gkm117

journal_volume

35

pub_type

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