NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription.
The nuclear factor of activated T cells (NFAT) plays a key role in gene transcription in both immune and non-immune cell types. Genetic ablation of individual NFAT proteins produces complex phenotypes in mice; in particular, NFAT1(-/-) and NFAT2(-/-) T cells show overproduction and underproduction of IL-4, respectively. We have taken a positive approach to the question of whether these two NFAT family members differentially regulate IL-4 gene transcription. Using constitutively-active NFAT proteins with alanine substitutions instead of phosphorylated serine residues in the regulatory domain, we find that NFAT1 and NFAT2 are both positive regulators of IL-4 gene transcription, intrinsically very similar in their ability to induce and sustain transcription of the IL-4 gene. Thus the disparate phenotypes of NFAT1(-/-) and NFAT2(-/-) T cells do not reflect differences in DNA-binding or transcriptional activity at the IL-4 gene, but most likely arise from differential regulation of the two proteins or other indirect effects.
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494006:NFATC2 protein, human; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma