CHARACTERIZATION OF INDUCIBLE DNASE-I HYPERSENSITIVE SITES FLANKING THE HUMAN INTERLEUKIN-5 GENE

Interleukin-5 (IL-5) production is necessary for eosinophilia associat ed with allergic conditions and parasitic infection. IL-5 mRNA is tran siently expressed by activated T-lymphocytes. In this report, we have analysed DNA regulatory regions associated with inducible IL-5 express ion in the human HSB-2 T-cell line. Only low levels of transcriptional activity were induced in cells transfected with up to 1.2 kb of DNA u pstream of the IL-5 gene. DNase I hypersensitivity analysis was employ ed to identify additional regulatory sequences located outside this re gion. Two hypersensitivity sites (HS) were identified, one 2.5 kb 5' a nd the other 1.6 kb 3' from the gene, that were induced on activation of HSB-2 cells by stimuli that induced IL-5 expression. The 5' site, b ut not the 3' site, was found in primary human T-cells. The presence o f the 5' HS did not always coincide with IL-5 expression. Inclusion of the region encompassing the 5' HS in promoter studies mediated a mode rate increase in transcriptional activity, suggesting that enhancer el ements essential for induction of maximal IL-5 transcription reside at a greater distance from the IL-5 gene. (C) 1998 Elsevier Science B.V. All rights reserved.