Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene.
The transcription factor NF-AT plays an essential role in the inducible transcription of several cytokine genes during T cell activation. The distal NF-AT site of the murine IL-2 promoter binds both NF-AT and AP-1 proteins, and thus represents a composite regulatory site that integrates Ca(2+)- and PKC-dependent signaling pathways in T cell activation. However, the individual contributions of the NF-AT and AP-1 components to promoter activity via this composite site have not been resolved, owing to the absence of a clearly defined AP-1 binding site, which, when mutated abolishes AP-1 binding. We describe here an apparently analogous NF-AT/AP-1 composite site in the murine IL-4 promoter, which can be mutated to selectively block the recruitment of each component. We show that the cooperative and coordinate involvement of both NF-AT and AP-1 is necessary for full activity of the NF-AT/AP-1 composite site, and, ultimately, the entire IL-4 promoter.
Rooney
J W
JW
Department of Genetics Harvard Medical School, Boston, Massachusetts 02115, USA.
Hoey
T
T
Glimcher
L H
LH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D051921:Fos-Related Antigen-2; D005796:Genes; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry; D018418:Th2 Cells; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D000099169:Fos-Related Antigen 1
D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; D007376:Interleukin-2; D015847:Interleukin-4; D046911:Macromolecular Substances; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C497873:Fosl2 protein, mouse