Distal regulatory elements play an important role in regulation of the human IL‐5 gene

• Published in: European journal of immunology Vol. 34; no. 12; pp. 3633 - 3643
• Main Authors: Urwin, Debra L., Schwenger, Gretchen T. F., Groth, David M., Sanderson, Colin J.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.12.2004
• Subjects: Base Sequence; Enhancer Elements, Genetic; Eosinophils; Gene Expression Regulation - physiology; Human IL‐5 gene; Humans; Interleukin-5 - genetics; Interleukin-5 - metabolism; Molecular Sequence Data; Promoter Regions, Genetic; Regulation; Sequence Analysis, DNA; Transcription, Genetic - physiology; Up-Regulation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425279

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.