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Title: The β7 integrin gene (Itgb-7) promoter is responsive to TGF-β1: Defining control regions
Authors: Lim, S.P. 
Leung, E.
Krissansen, G.W.
Keywords: β7 integrin gene
Promoter elements
Issue Date: 1998
Citation: Lim, S.P., Leung, E., Krissansen, G.W. (1998). The β7 integrin gene (Itgb-7) promoter is responsive to TGF-β1: Defining control regions. Immunogenetics 48 (3) : 184-195. ScholarBank@NUS Repository.
Abstract: The β7 integrins LPAM-1 (α4β7) and M290 (αEβ7) mediate the homing of lymphocytes to gut-associated lymphoid tissue, and the proposed retention of intraepithelial lymphocytes (IEL), respectively. Here we show that the gut mucosal cytokine TGF- β1 increases the expression of β7 and αE subunit mRNA transcripts and the cell-surface expression of M290 on T cells, and that it decreases the level of α4 integrin transcripts. Induced β7 integrin gene expression was inhibited by the protein tyrosine kinase inhibitor genistein, implicating a role for tyrosine phosphorylation. An analysis of the P7 integrin gene promoter revealed three DNAse I hypersensitivity sites, two of which mapped to the 5' and 3' ends of a promoter fragment (nucleotides + 690 to +63) that directed both the basal and the TGF-β1-induced expression of a heterologous reporter gene. Deletion analysis identified two TGF-β1 response regions encompassing nucleotides -509 to -398 (TGFBRR1), and -122 to +32 (TGFBRR2). TGFBRR1 interacted with at least five protein complexes, whose binding could be induced with TGF-β1 stimulation and could be antagonized by TGFBRR2 which harbored both similar and distinctive cis-elements. TGFBRR2 interacted specifically with at least two major nuclear protein complexes, whose binding was phosphorylation dependent. These data provide new insights into the mechanism by which TGF-β may switch LPAM-1(+ ve) migrating T cells to express M290, facilitating their retention in the gut.
Source Title: Immunogenetics
ISSN: 00937711
DOI: 10.1007/s002510050422
Appears in Collections:Staff Publications

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