fos-mediated repression of cardiac myosin light chain-2 gene transcription.
The transcription of the chicken cardiac myosin light chain-2 (MLC-2) promoter containing a 1.3 Kb 5'-flanking DNA segment is repressed upon co-transfection with an expression vector (pMMV) containing the proto-oncogene fos in embryonic chicken cardiac muscle cells in culture. Similar concentrations of co-transfectants containing other genes e.g. luciferase were ineffective. To identify the DNA element(s) in MLC-2 gene that responds to fos-mediated inhibition, 5'-sequential deletion mutants of MLC-2 promoter were tested in a transient transfection assay. A mutant, in which the 5' distal sequence was deleted upto -1200 bp upstream of the mRNA start site was sensitive to fos inhibition, but the mutant containing -1130 bp was not, suggesting that a fos responsive element (FRE) is located between -1130 to -1200 bp upstream of the transcription initiation site. The same FRE sequence was also responsive to fos-inhibition in chicken skeletal muscle cells as well. Since over-expression of fos is implicated in repression of myogenic process, the selective inhibition of MLC-2 promoter activity by fos and identification of FRE sequence potentially important in understanding the relationship between myogenesis and the oncoprotein-mediated signal pathway(s).
Goswami
S K
SK
Department of Anatomy and Cell Biology, State University of New York Health Science Center, Brooklyn 11203.
Zarraga
A M
AM
Martin
M E
ME
Morgenstern
D
D
Siddiqui
M A
MA
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D016762:Genes, fos; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection / Q000235:genetics
D004247:DNA; D009218:Myosins