Regulation of rat brain natriuretic peptide transcription. A potential role for GATA-related transcription factors in myocardial cell gene expression.
GATA-binding proteins are transcription factors that regulate the stage- and tissue-specific expression of globin genes in cells of the erythroid lineage. Recently, a cardiac GATA-binding protein was found to be the earliest gene expressed during cardiogenesis; however, the target genes of this transcription factor in the heart are unknown. Since brain natriuretic peptide (BNP) is activated early in cardiac growth and development, we evaluated whether it could serve as a target gene for GATA-binding protein-mediated induction. Upon isolating and sequencing 2.5 kilobases of the rat BNP 5'-flanking sequence (FS), a variety of putative transcriptional enhancer sites were identified, including several GATA consensus sequences (WGATAR), one of which apparently serves as the major promoter site. Primary myocardial cells were transfected with BNP/luciferase fusion genes; reporter expression was strongly induced by typical growth factors such as phorbol esters, serum, or alpha 1-adrenergic agonists, as well as by GATA-4 overexpression. Truncation analyses showed that inducibility mapped primarily to the proximal -116 base pair of the rat BNP 5'-FS, where there are two consensus GATA sites in addition to the GATA sequence at the TATA box. Point mutation analyses showed that at least one of the GATA sites was required to confer full GATA-4-inducible transcription. These results demonstrate that a proximal region of the rat BNP 5'-FS is required for growth factor- and GATA-inducible transcription, supporting the view that the BNP gene could serve as a target for GATA-binding proteins during early cardiac development.
Department of Biology, San Diego State University, California 92182.
D J
DJ
Thuerauf
D S
DS
Hanford
C C
CC
Glembotski
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D004247:DNA; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D020097:Natriuretic Peptide, Brain; D004247:DNA