Dt. Nellesen et al., Discrete enhancer elements mediate selective responsiveness of enhancer ofsplit complex genes to common transcriptional activators, DEVELOP BIO, 213(1), 1999, pp. 33-53
In Drosophila, genes of the Enhancer of split Complex [E(spl)-C] are import
ant components of the Notch (N) cell-cell signaling pathway, which is utili
zed in imaginal discs to effect a series of cell fate decisions during adul
t peripheral nervous system development. Seven genes in the complex encode
basic helix-loop-helix (bHLH) transcriptional repressors, while 4 others en
code members of the Bearded family of small proteins. A striking diversity
is observed in the imaginal disc expression patterns of the various E(spl)-
C genes, suggestive of a diversity of function, but the mechanistic basis o
f this variety has not been elucidated. Here we present strong evidence fro
m promoter-reporter transgene experiments that regulation at the transcript
ional level is primarily responsible. Certain E(spl)-C genes were known pre
viously to be direct targets of transcriptional activation both by the N-si
gnal-dependent activator Suppressor of Hairless [Su(H)] and by the proneura
l bHLH proteins achaete and scute. Our extensive sequence analysis of the p
romoter-proximal upstream regions of 12 transcription units in the E(spl)-C
reveals that such dual transcriptional activation is likely to be the rule
for at least 10 of the 12 genes. We next show that the very different wing
imaginal disc expression patterns of E(spl)m4 and E(spl)my are a property
of small (200-300 bp), evolutionarily conserved transcriptional enhancer el
ements, which can confer these distinct patterns on a heterologous promoter
despite their considerable structural similarity [each having three Su(H)
and two proneural protein binding sites]. We also demonstrate that the char
acteristic inactivity of the E(spl)my enhancer in the notum and margin terr
itories of the wing disc can be overcome by elevated activity of the N rece
ptor. We conclude that the distinctive expression patterns of E(spl)-C gene
s in imaginal tissues depend to a significant degree on the capacity of the
ir transcriptional cis-regulatory apparatus to respond selectively to direc
t proneural- and Su(H)-mediated activation, often in only a subset of the t
erritories and cells in which these modes of regulation are operative. (C)
1999, Academic Press.