title: Distal regulatory elements play an important role in regulation of the human IL-5 gene.
abstract: Eosinophil infiltration of the lung is a feature of both allergic and nonallergic asthma, and IL-5 is the key cytokine regulating the production and activation of these cells. Despite many studies focusing on the IL-5 promoter in both humans and mice there is as yet no clear picture of how the IL-5 gene is regulated. The aim of this study was to determine if distal regulatory elements contribute to appropriate regulation of the human IL-5 (hIL-5) gene. Activity of the -507/+44 hIL-5 promoter was compared to expression of the endogenous IL-5 gene in PER-117 T cells. The IL-5 promoter was not sufficient to reproduce a physiological pattern of IL-5 expression. Further, functional analysis of the 5' and 3' intergenic regions revealed a number of novel regulatory elements. We have identified a conserved enhancer located approximately 6.2 kb upstream of the hIL-5 gene. This region contains two potential GATA-3-binding sites and increases expression from the hIL-5 promoter by up to ninefold.
authors.affiliation: Western Australian Biomedical Research Institute and the School of Biomedical Sciences, Curtin University of Technology, Perth, Australia. durwin@biomail.ucsd.edu
authors.forename: Debra L
authors.initials: DL
authors.lastname: Urwin
authors.forename: Gretchen T F
authors.initials: GT
authors.lastname: Schwenger
authors.forename: David M
authors.initials: DM
authors.lastname: Groth
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Sanderson
mesh_terms: D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation
chemical_list: D015848:Interleukin-5