Positive transcriptional regulatory element located within exon 1 of elastin gene

• Published in: American journal of physiology. Lung cellular and molecular physiology 2006-09, Vol.291 (3), p.35
• Main Authors: Pierce, Richard A, Moore, Carla H, Meltem Cevik Arikan
• Format: Article
• Language: English
• Subjects: Cells; Genes; Genomics; Lungs
• ISSN: 1040-0605; 1522-1504

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'-flanldng 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 Spi 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. [PUBLICATION ABSTRACT]