title: The mouse beta 7 integrin gene promoter: transcriptional regulation of the leukocyte integrins LPAM-1 and M290.
abstract: The leukocyte adhesion receptors M290 (alpha M290/beta 7) and LPAM-1 (alpha 4 beta 7) comprise the beta 7-subfamily of integrins, which are constitutively 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 beta 7 integrins are regulated during an immune response, we isolated and characterized the promoter region of the beta 7 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 lymphoid lineages. Multiple retinoic acid receptor sites for steroid/thyroid hormone receptors which typify the leukocyte cell adhesion molecule subset of integrins are present. The beta 7 promoter, like its alpha 4 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 beta 7 promoter parallels the complex regulation of expression of M290 and LPAM-1 in inflammation and gut mucosal immunity.
authors.affiliation: Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
authors.forename: E
authors.initials: E
authors.lastname: Leung
authors.forename: P E
authors.initials: PE
authors.lastname: Mead
authors.forename: Q
authors.initials: Q
authors.lastname: Yuan
authors.forename: W M
authors.initials: WM
authors.lastname: Jiang
authors.forename: J D
authors.initials: JD
authors.lastname: Watson
authors.forename: G W
authors.initials: GW
authors.lastname: Krissansen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics*; D007421:Intestine, Small / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D000951:Antigens, Neoplasm; D039641:Integrin beta Chains; D016023:Integrins; C091368:integrin beta7; D004247:DNA