Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: Possible interaction withpolycomb and trithorax group proteins
F. Hirose et al., Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: Possible interaction withpolycomb and trithorax group proteins, MOL CELL B, 21(21), 2001, pp. 7231-7242
The promoters of Drosophila genes encoding DNA replication-related proteins
contain transcription regulatory element DRE (5'-TATCGATA) in addition to
E2F recognition sites. A specific DRE-binding factor, DREF, positively regu
lates DRE-containing genes. In addition, it has been reported that DREF can
bind to a sequence in the hsp70 scs' chromatin boundary element that is al
so recognized by boundary element-associated factor, and thus DREF may part
icipate in regulating insulator activity. To examine DREF function in vivo,
we established transgenic flies in which ectopic expression of DREF was ta
rgeted to the eye imaginal discs. Adult flies expressing DREF exhibited a s
evere rough eye phenotype. Expression of DREF induced ectopic DNA synthesis
in the cells behind the morphogenetic furrow, which are normally postmitot
ic, and abolished photoreceptor specifications of R1, R6, and R7. Furthermo
re, DREF expression caused apoptosis in the imaginal disc cells in the regi
on where commitment to R1/R6 cells takes place, suggesting that failure of
differentiation of R1/R6 photoreceptor cells might cause apoptosis. The DRE
F-induced rough eye phenotype was suppressed by a half-dose reduction of th
e E2F gene, one of the genes regulated by DREF, indicating that the DREF ov
erexpression phenotype is useful to screen for modifiers of DREF activity.
Among Polycomb/trithorax group genes, we found that a half-dose reduction o
f some of the trithorax group genes involved in determining chromatin struc
ture or chromatin remodeling (brahma, moira, and osa) significantly suppres
sed and that reduction of Distal-less enhanced the DREF-induced rough eye p
henotype. The results suggest a possibility that DREF activity might be reg
ulated by protein complexes that play a role in modulating chromatin struct
ure. Genetic crosses of transgenic flies expressing DREF to a collection of
Drosophila deficiency stocks allowed us to identify several genomic region
s, deletions of which caused enhancement or suppression of the DREF-induced
rough eye phenotype. These deletions should be useful to identify novel ta
rgets of DREF and its positive or negative regulators.