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Positive transcriptional regulatory element located within exon 1 of elastin gene

¹Division of Pulmonary Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; and ²Department of Infectious Diseases, University of Massachusetts Medical School, Worchester, Massachusetts

Submitted 23 November 2004 ; accepted in final form 1 March 2006

Elastin gene transcription is cell type specific and developmentally regulated, but the promoter often exhibits relatively weak activity in transient transfections of cells that express elastin at high levels. To search for positive-acting regulatory sequences, we isolated genomic clones spanning the mouse elastin gene and extensive 5'- and 3'-flanking regions. Restriction fragments of potential regulatory regions were ligated 5' or 3' relative to the active promoter to test for enhancer activity in transient transfections of fetal rat lung fibroblasts, which express elastin at high levels, and distal lung epithelial cells, which do not express detectable elastin. Fragments of intron 1 did not exhibit significant enhancer activity. Inclusion of the 84-bp exon 1 and adjacent 5'-untranslated region increased activity of the elastin promoter approximately sixfold compared with parental constructs. Transfections with constructs of varying promoter length showed that as little as 40 bp of the 5' end of exon 1 confers enhanced activity in elastin-expressing rat lung fibroblasts, but these constructs had variable activity in lung epithelial cell lines. This region, localized between the transcription start site and extending into exon 1, binds Sp1 in nuclear extracts from elastin-expressing cells. These studies indicate a role for the 5' end of the first exon of the elastin gene in regulating strong transcriptional activity in elastogenic cells.

promoter; lung