c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter.
The c-myb proto-oncogene product (c-Myb) is a transcriptional activator that can bind to the specific DNA sequences. Although c-Myb also represses an artificial promoter containing the Myb binding sites, natural target genes transcriptionally repressed by c-Myb have not been identified. We have found that the human c-erbB-2 promoter activity is repressed by c-Myb or B-Myb in a chloramphenicol acetyltransferase co-transfection assay. Domain analyses of c-Myb suggested that Myb represses the c-erbB-2 promoter activity by competing with positive regulators of the c-erbB-2 promoter. In in vitro transcription assays, Myb proteins containing only the DNA binding domain could repress c-erbB-2 promoter activity. Two Myb binding sites in the c-erbB-2 promoter were critical for transcriptional repression by c-Myb. One of the two Myb binding sites overlaps the TATA box, and DNase I footprint analyses indicated that c-Myb can compete with TFIID. These results suggest that Myb-induced trans-repression of the c-erbB-2 promoter partly involves competition between Myb and TFIID.
Mizuguchi
G
G
Laboratory of Molecular Genetics, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Kanei-Ishii
C
C
Takahashi
T
T
Yasukawa
T
T
Nagase
T
T
Horikoshi
M
M
Yamamoto
T
T
Ishii
S
S
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012097:Repressor Proteins / Q000502:physiology*
D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; C000715470:MAS1 protein, human