Influence Of Histone Acetyltransferase CBP/p300 On Interleukin-5 Gene Expression Regulation And Its Molecular Mechanisms

Interleukin-5 (IL-5), expressed primarily by type-2 T helper (Th2) cells, plays an essential role in the development of allergic diseases includeing allergic asthma. Histone acetyltransferase CBP/p300 remodels chromatin by acetylating histones resulting in open structure of chromatin and active transcription. Adenovirus protein E1A inhibits the activity of CBP/p300. In this study, we analyzed the effects of E1A on IL-5 gene promoter/luciferase reporter activity. The results showed that El A protein inhibited the activity of PMA/ionomycin-stimulated IL-5 gene promoter/luciferase reporter construct. In contrast, overexpression of the CBP/p300-binding defective El A A2-36 protein did not inhibit IL-5 gene promoter activity. El A protein can modulate CBP/p300 function to activate the transcription of IL-5 gene promoter/luciferase reporter plasmid. Transcriptional coactivator CBP/p300 and transcription factors C/EBPp, NF-AT, and c-Fos synergistically activated IL-5 promoter. Furthermore, we found that ectopic expression of p300 increased endogenous IL-5 mRNA expression. The histone acetyltransferase activity of CBP/p300 was required to activate IL-5 expression. In chromatin immunoprecipitation assay (ChIP), we found that CBP/p300 could acetylate histones on IL-5 promoter, resulting in increased accessibility of the open chromatin to the transcriptional machinery and therefore promoted gene transcription. Moreover, we showed that CBP/p300 acetylated the transcription factor C/EBP, resulting in an increased transactivation activity of the C/EBP. These data demonstrated for the first time that histone acetyltransferase CBP/p300 was involved in the activation of IL-5 gene expression and the HAT activity was important in regulation of IL-5 expression. This study provides further insight into the mechanisms of transcriptional regulation of IL-5 gene.