Studies on transcriptional regulation of the mucosal T-cell integrin alphaEbeta7 (CD103).
Integrin alphaEbeta7 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-beta (TGF-beta). In mice, mRNA for the alphaE subunit was found to be abundant in mucosal T cells but absent from other tissues. Exposure of a T-cell line to TGF-beta strongly up-regulated alphaE mRNA levels within 30 min, and nuclear run-on experiments established that regulation occurred at the level of transcription. The organization of the human alphaE gene and a very closely linked novel gene, ELG, was determined. The alphaE promoter was tested in T cells and fibroblasts and functioned equally well in both cell types and did not confer TGF-beta 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 alphaE gene revealed one hypersensitive site, found only in alphaE+ cells, located near the transcription start points. These results show that, unlike the situation with other integrins, lineage specificity and cytokine responsiveness of alphaE transcription are not conferred by the proximal promoter. Specificity may depend on distant control elements that have not yet been identified.
Robinson
P W
PW
The Babraham Institute, Babraham, Cambridge, UK.
Green
S J
SJ
Carter
C
C
Coadwell
J
J
Kilshaw
P J
PJ
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D003850:Deoxyribonuclease I / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D039001:Integrin alpha Chains; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D039001:Integrin alpha Chains; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; D003850:Deoxyribonuclease I