THE MOUSE BETA-7 INTEGRIN GENE PROMOTER - TRANSCRIPTIONAL REGULATION OF THE LEUKOCYTE INTEGRINS LPAM-1 AND M290

The leukocyte adhesion receptors M290 (alphaM290/beta7) and LPAM-1 (al pha4beta7) comprise the beta7-subfamily of integrins, which are consti tutively expressed on subsets of lymphocytes populating the mouse smal l intestine. They are induced de novo after in vitro activation of lym phocytes and hence may serve a more general role in inflammation. In o rder to understand how beta7 integrins are regulated during an immune response, we isolated and characterized the promoter region of the bet a7 gene. Primer extension and rapid amplification of cDNA ends identif ied one major transcriptional start site in a favourable context, whic h resembles the initiator of terminal deoxynucleotidyl transferase. Tr ansfection assays with a luciferase reporter gene revealed that cell-s pecific expression in vitro was retained in a 292 bp sequence, which c ontained several consensus binding motifs for transcriptional factors preferentially expressed in cells of the lymphoid lineages. Multiple r etinoic acid receptor sites for steroid/thyroid hormone receptors whic h typify the leukocyte cell adhesion molecule subset of integrins are present. The beta7 promoter, like its alpha4 chain partner, contains t he E box core sequence CACCTG found within the muscle creatine kinase enhancer which binds MyoD in vitro. The number of potential DNA bindin g sites for transcriptional factors in the beta7 promoter parallels th e complex regulation of expression of M290 and LPAM-1 in inflammation and gut mucosal immunity.