Interleukin-4 (IL-4) is an important immunoregulatory cytokine with diverse effects on immune system maturation and function. Two major cell types are known to produce IL-4, T cells and mast cells. The regulation of IL-4 gene expression in these cell types has been shown to be different and a regulatory element in the second intron of the gene is mast cell specific, contributing to the different mechanisms of regulation in the two cell types. This project is based on a report that mast cells express a truncated IL-4 mRNA, encompassing only exons 3 and 4. This truncated mRNA was only detected by RNAse protection assays as Northern blot analysis was not sufficiently sensitive to distinguish the truncated mRNA from the full length mRNA. Analysis of intronic DNA has revealed the presence of a """"""""TATA-less"""""""" promoter elements, suggesting that transcription of this truncated mRNA may initiate in this intronic regulatory element. This project is focused on further characterizing this truncated transcript and assessing the possible biological consequences of its expression.
The aims are: 1) to assess the expression profile of the truncated transcript; 2) to assess the function of the transcript and 3) to define the regulatory elements within the intron that regulate transcription of the truncated mRNA. As it is possible that this novel transcript may represent an important mechanism for regulating IL-4 gene expression and for understanding the mechanisms behind its expression and by which it may regulate IL-4 biological activity.
| Hural, J A; Kwan, M; Henkel, G et al. (2000) An intron transcriptional enhancer element regulates IL-4 gene locus accessibility in mast cells. J Immunol 165:3239-49 |
| Brown, M A; Hural, J (1997) Functions of IL-4 and control of its expression. Crit Rev Immunol 17:1-32 |
| Henkel, G; Brown, M A (1994) PU.1 and GATA: components of a mast cell-specific interleukin 4 intronic enhancer. Proc Natl Acad Sci U S A 91:7737-41 |
