The mouse β7 integrin gene promoter: Transcriptional regulation of the leukocyte integrins LPAM-1 and M290

Abstract

The leukocyte adhesion receptors M290 (αM290/β7) and LPAM-1 (α4β7) comprise the β7-subfamily of integrins, which are constitutlvely expressed on subsets of lymphocytes populating the mouse small intestine. They are induced de novo after in vitro activation of lymphocytes and hence may serve a more general role in inflammation. In order to understand how β7 integrins are regulated during an immune response, we isolated and characterized the promoter region of the β7 gene. Primer extension and rapid amplification of cDNA ends identified one major transcriptional start site in a favourable context, which resembles the initiator of terminal deoxynucleotidyl transferase. Transfection assays with a luciferase reporter gene revealed that cell-specific expression in vitro was retained in a 292 bp sequence, which contained several consensus binding motifs for transcriptional factors preferentially expressed in cells of the lymphold lineages. Multiple retinoic acid receptor sites for steroid/thyroid hormone receptors which typify the leukocyte cell adhesion molecule subset of integrins are present. The β7 promoter, like its α4 chain partner, contains the E box core sequence CACCTG found within the muscle creatine kinase enhancer which binds MyoD in vitro. The number of potential DNA binding sites for transcriptional factors in the β7 promoter parallels the complex regulation of expression of M290 and LPAM-1 in inflammation and gut mucosal immunity. © 1993 Oxford University Press.