title: CCAAT/enhancer-binding protein alpha (C/EBPalpha) is critical for interleukin-4 expression in response to FcepsilonRI receptor cross-linking.
abstract: Basophils mediate many of their biological functions by producing IL-4. However, it is unknown how the Il4 gene is regulated in basophils. Here, we report that CCAAT/enhancer-binding protein α (C/EBPα), a major myeloid transcription factor, was highly expressed in basophils. We show that C/EBPα selectively activated Il4 promoter-luciferase reporter gene transcription in response to IgE cross-linking, but C/EBPα did not activate other known Th2 or mast cell enhancers. We found that the PI3K pathway and calcineurin were essential in C/EBPα-driven Il4 promoter-luciferase gene transcription. Our mutation analyses revealed that C/EBPα drove Il4 promoter-luciferase activity depending on its DNA binding domain. Mutation of the C/EBPα-binding site in the Il4 promoter region abolished C/EBPα-driven Il4 promoter-luciferase activity. Our results further showed that a mutation in nuclear factor of activated T cells (NFAT)-binding sites in the Il4 promoter also negated C/EBPα-driven Il4 promoter-luciferase activity. Our study demonstrates that C/EBPα, in cooperation with NFAT, directly regulates Il4 gene transcription.
authors: Division of Allergy and Immunology, Department of Medicine, National Jewish Health, University of Colorado Denver School of Medicine, Denver, Colorado 80206, USA.
authors: Xiaopeng
authors: X
authors: Qi
authors: Jun
authors: J
authors: Nishida
authors: Lee
authors: L
authors: Chaves
authors: Keitaro
authors: K
authors: Ohmori
authors: Hua
authors: H
authors: Huang
mesh_terms: D000818:Animals; D001491:Basophils / Q000166:cytology / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D007152:Immunologic Capping / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D050778:NFATC Transcription Factors; D017455:Receptors, IgE; D015847:Interleukin-4