Multiple Transcription Factors Are Required for Activation of Human Interleukin 9 Gene in T Cells

Abstract

The genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappaB, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells.

Nuclear Factor of Activated T Cells 1 (NFAT1)-induced Permissive Chromatin Modification Facilitates Nuclear Factor-κB (NF-κB)-mediated Interleukin-9 (IL-9) Transactivation

“…NF-B has also been implicated in IL-9 expression in mouse macrophage cells upon LPS stimulation (46). Also, binding of NF-B to the human IL-9 promoter in T cells has been demonstrated (24,47). However, the role of NF-B in regulating IL-9 expression in mouse Th9 cell is still unknown.…”

IL-9 and IL-13 Production by Activated Mast Cells Is Strongly Enhanced in the Presence of Lipopolysaccharide: NF-κB Is Decisively Involved in the Expression of IL-9

“…virus type I, an NF-B site at Ϫ59 to Ϫ50 was shown to be involved in basal and PHA-induced expression of the IL-9 gene (45). Using the TRANSFAC database (www.transfac.gbf-braunschweig.de), we identified three potential binding sites for NF-B within the murine IL-9 promoter, termed NF-B1-3.…”

IL-9 in Allergic Inflammation

“…Within this region, an NF-ĸB site and its adjacent 20-bp upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-ĸB, c-Jun and potentially new proteins (around 35 kD) can bind to this important sequence [7]. Therefore it seems that the cooperation of different transcription factors is essential for IL-9 gene expression.…”

“…In human T cell leukemia virus type I-transformed human T cells, C5MJ2, a proximal region of the IL-9 promoter (34 bp, between –46 and –80) was found to be the minimum sequence for basal and inducible expression of the IL-9 gene [7]. Within this region, an NF-ĸB site and its adjacent 20-bp upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity.…”