Mary Zutter
Faculty Member
Last active: 4/26/2016

The human alpha 2 integrin gene promoter. Identification of positive and negative regulatory elements important for cell-type and developmentally restricted gene expression.

Zutter MM, Santoro SA, Painter AS, Tsung YL, Gafford A
J Biol Chem. 1994 269 (1): 463-9

PMID: 8276836

The alpha 2 beta 1 serves as a collagen receptor or a collagen/laminin receptor, depending upon cell type. Expression of the integrin is regulated during normal cellular differentiation and is altered during carcinogenesis. We have previously demonstrated that increased expression of the alpha 2 beta 1 integrin during megakaryocytic differentiation is a consequence of increased alpha 2 mRNA due to transcriptional activation of the alpha 2 integrin gene and that the decreased expression of the integrin in breast adenocarcinoma is due to decreased steady-state levels of alpha 2 mRNA. We now report the identification and characterization of the 5'-flanking region of the alpha 2 integrin gene. The 5'-untranslated region of the alpha 2 mRNA extends 129 base pairs 5' to the site of translation initiation. The promoter region lacks TATA and CAAT boxes but contains an abbreviated initiator sequence and six Sp1 binding sites. Consensus binding sites for AP-1 and AP-2 complexes, a GATA box, a Pu.1 box, and two palindromic motifs with potential to bind the estrogen receptor are also present. A 961-base pair fragment of the 5'-flanking region directs both cell type- and differentiation-specific expression of a reporter gene in T47-D epithelial cells and in pluripotent hematopoietic K562 cells upon megakaryocytic differentiation.

MeSH Terms (14)

Amino Acid Sequence Base Sequence Binding Sites Cell Line DNA, Complementary Gene Expression Regulation Humans Integrin alpha2 Integrins Molecular Sequence Data Promoter Regions, Genetic Protein Biosynthesis Transcription Factors Tumor Cells, Cultured

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