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This Article Full Text Full Text (PDF) All Versions of this Article: 287/1/L52    most recent 00430.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Ding, W. Articles by Warburton, D. Search for Related Content PubMed PubMed Citation Articles by Ding, W. Articles by Warburton, D.

Genomic structure and promoter characterization of the human Sprouty4 gene, a novel regulator of lung morphogenesis

Developmental Biology Program, Saban Research Institute, Childrens Hospital Los Angeles, Department of Pediatric Surgery, University of Southern California Keck School of Medicine and School of Dentistry, Los Angeles, California 90027

Submitted 4 December 2003 ; accepted in final form 17 February 2004

The expression of Sprouty4 (Spry4), an intracellular FGF receptor antagonist, shows a temporally and spatially restricted pattern in embryonic lung and is induced by ERK signaling. To clarify the molecular mechanisms regulating Spry4 transcription, the genomic structure of the human Sprouty4 (hSpry4) gene was first determined by using the GenomeWalker kit. The hSpry4 gene spans > 14 kb and is organized in three exons and two introns. Multiple transcription start sites were subsequently mapped by 5'-rapid amplification of cDNA ends. Analysis of up to 4 kb of sequence in the 5'-flanking region of the gene showed the presence of multiple potential transcription factor binding sites but no TATA or CAAT boxes. Transient transfection using luciferase reporter gene constructs with progressive deletions of the hSpry4 5'-flanking region revealed that the core promoter activity is located within the proximal 0.4-kb region, whereas the minimal ERK-inducible promoter activity is between –69 and –31. Homology analysis further showed that the core promoter region of the hSpry4 gene exhibits significant similarity to the 5'-flanking region of the mouse gene.

lung development; transcription initiation site; homology analysis; reporter gene assay; transcription factor binding site