Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease.

摘要: Abstract The epidermal growth factor (EGF) receptor is the functional target of mitogen EGF and cellular homolog avian erythroblastosis virus erbB oncogene product. Regulation expression proto-oncogene encoding can be elucidated by studying structure function gene promoter outside confines cell. Previously, we reported isolation human promoter. The highly GC rich, contains no TATA or CAAT box, has multiple transcription start sites. An S1 nuclease-sensitive site now been found 80 to 110 base pairs (bp) upstream from major in vivo initiation site. Two sets direct repeat sequences were this area; both conform motif TCCTCCTCC. When deletion mutations made region using either Bal 31 exonuclease nuclease, that activity dropped three- fivefold, on basis transient-transfection analysis. Examination nuclear protein binding normal mutated DNAs gel retardation analysis DNase I footprinting revealed two specific factors bind but cannot nuclease-mutated One Sp1. results suggest these trans-acting interact with directly indirectly stimulate transcription.