In the course of analyzing the murine c-myc promoter response to glucocorti
coid, we have identified a novel glucocorticoid response element that does
not conform to the consensus glucocorticoid receptor-binding sequence. This
c-myc promoter element has the sequence CAGGGTACATGGCGTATGTGTG, which has
very little sequence similarity to any known response element. Glucocortico
ids activate c-myc/reporter constructs that contain this element. Deletion
of these sequences from the c-myc promoter increases basal activity of the
promoter and blocks glucocorticoid induction. Insertion of this element int
o SV40/reporters inhibits basal reporter gene activity in the absence of gl
ucocorticoids. Glucocorticoids stimulate activity of reporters that contain
this element. Recombinant glucocorticoid receptor binds to this element in
vitro. An unidentified cellular repressor also binds to this element. The
activated glucocorticoid receptor displaces this protein(s). We conclude th
at the glucocorticoid receptor binds to the c-myc promoter in competition w
ith this protein, which is a repressor of transcription. To our knowledge,
no glucocorticoid response element with such properties has ever been repor
ted.