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Papers In Press, published online ahead of print August 1, 2002
Cardiovascular Research, Berlex Biosciences, Richmond, CA 94804-0099
Corresponding Author: junliang_pan{at}berlex.com
Corin is a multiple domain type II transmembrane serine protease highly expressed in the heart. It converts pro-atrial natriuretic peptide (pro-ANP) to ANP, a cardiac hormone that regulates blood volume and pressure. Here we describe the genomic structures of the human and murine corin genes and functional analysis of their promoters. Both corin genes contain 22 exons and span >200 kb. Their intron/exon boundaries are well conserved with most exons encoding distinct structural domains, supporting the idea that corin evolved as a result of exon duplication and rearrangement. Comparison of the 5’-flanking regions of the human and murine corin genes revealed several conserved sequences including binding sites for Tbx5, GATA, Nkx-2.5 and Krüppel-like transcription factors. Transfection experiments with reporter gene constructs driven by the human or murine corin 5’-flanking regions indicated that the sequence from –405 to –15 in human or –646 to –77 in mouse was sufficient to promote high levels of gene expression in murine cardiomyocytes. In contrast, these sequences produced only minimal levels of expression in HeLa cells. Within these sequences, we identified a conserved GATA element that bound to GATA-4. Mutation in the core sequence impaired both GATA-4 binding and gene expression. These data indicate that the GATA element and its binding to GATA-4 are essential for cardiac expression of the human and murine corin genes.
J. Biol. Chem, 10.1074/jbc.M205686200
Submitted on June 8, 2002
Revised on July 22, 2002
Accepted on August 1, 2002
Human and murine corin genes: Genomic structures and functional GATA elements in their promoters
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