Integrin αEβ7 is expressed almost exclusively by mucosal T cells and mucosal dendritic antigen-presenting cells (APCs) and is thought to be induced locally by transforming growth factor-β (TGF-β). In mice, mRNA for the αE subunit was found to be abundant in mucosal T cells but absent from other tissues. Exposure of a T-cell line to TGF-β strongly up-regulated αE mRNA levels within 30 min, and nuclear run-on experiments established that regulation occurred at the level of transcription. The organization of the human αE gene and a very closely linked novel gene, ELG, was determined. The αE promoter was tested in T cells and fibroblasts and functioned equally well in both cell types and did not confer TGF-β responsiveness. Regions of the promoter providing enhancer activity and phorbol 12-myristate 13-acetate (PMA) responsiveness were identified by deletion studies. DNAse 1 hypersensitivity analysis of 36 kb of the αE gene revealed one hypersensitive site, found only in αE+ cells, located near the transcription start points. These results show that, unlike the situation with other integrins, lineage specificity and cytokine responsiveness of αE transcription are not conferred by the proximal promoter. Specificity may depend on distant control elements that have not yet been identified.