Novel CD28-responsive enhancer activated by CREB/ATF and AP-1 families in the human interleukin-2 receptor alpha-chain locus.
The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the alpha chain CD25/IL-2Ralpha is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Ralpha gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Ralpha gene transcription. By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5' of the IL-2Ralpha gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Ralpha gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.
Yeh
J H
JH
INSERM U119-IFR57, 13009 Marseilles, France.
Lecine
P
P
Nunes
J A
JA
Spicuglia
S
S
Ferrier
P
P
Olive
D
D
Imbert
J
J
D051696:Activating Transcription Factors; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018076:DNA, Complementary; D004742:Enhancer Elements, Genetic; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D051696:Activating Transcription Factors; D001798:Blood Proteins; D018106:CD28 Antigens; D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018808:Transcription Factor AP-1; D014157:Transcription Factors