N. Kirov et al., CONVERSION OF A SILENCER INTO AN ENHANCER - EVIDENCE FOR A CO-REPRESSOR IN DORSAL-MEDIATED REPRESSION IN DROSOPHILA, EMBO journal, 12(8), 1993, pp. 3193-3199
The dorsal (dl) protein gradient determines patterns of gene expressio
n along the dorsal-ventral axis of the Drosophila embryo. dl protein i
s at peak levels in ventral nuclei of the embryo where it activates so
me genes (twist and snail) and represses others [zerknullt (zen), deca
pentaplegic and tolloid]. It is a member of the rel family of transcri
ption factors and interacts with specific DNA sequences in the regulat
ory regions of its target genes. These sequences (dl binding sites), w
hen taken from the context of either an activated or repressed promote
r, mediate transcriptional activation of a heterologous promoter, but
not repression. We found that T-rich sequences close to the dl binding
sites in the silencer region of the zen promoter are conserved betwee
n three Drosophila species. Using this sequence information we defined
a minimal element that can mediate repression of a heterologous promo
ter. This element interacts with at least two factors present in embry
onic extracts, one of which is dl protein. The other factor binds to t
he T-rich site. Point mutations in either site abolish ventral repress
ion in vivo. In addition, mutations in the T-rich site cause ectopic e
xpression in ventral regions indicating that the minimal silencer was
converted into an enhancer.