Characterization of three different elements in the 5′-flanking region of the fibronectin gene which mediate a transcriptional response to cAMP

Christopher Bowlus, Jay J. McQuillan, Douglas C. Dean

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

A cAMP regulatory element (CRE) at nucleotide position - 170 of the fibronectin gene was characterized previously (Dean, D. C., Blakeley, M. S., Newby, R. F., Ghazal, P., Hennighausen, L., and Bourgeois, S. (1989) Mol. Cell. Biol. 9, 1498-1506). Here we identify two additional low affinity CREs at nucleotide positions -260 and -415 which differ in sequence by 1 base pair. Interestingly, these CREs did not compete for binding of nuclear proteins in gel retardation assays, and partial tryptic digestion of protein-DNA complexes produced a different pattern with each CRE, indicating that they bind different proteins. CRE (-170) competed for binding of proteins to both CREs, suggesting that it may represent a composite of the two elements. CRE (-415) competed effectively for binding of nuclear proteins to the somatostatin gene CRE, suggesting that, like the somatostatin CRE, it binds the nuclear protein CREB. On the other hand, CRE (-260) appears to bind the nuclear protein PEA-2, which also binds a site in the polyoma virus enhancer. In summary, disruption of dyad symmetry in the 3′ region of the CRE, as occurs with CRE (-260) and CRE (-415), results in a lower affinity site and may also change the specificity for different nuclear proteins.

Original languageEnglish (US)
Pages (from-to)1122-1127
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number2
StatePublished - Jan 15 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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