Ectopic Expression of DREF Induces DNA Synthesis, Apoptosis, and Unusual Morphogenesis in the Drosophila Eye Imaginal Disc: Possible Interaction with Polycomb and trithorax Group Proteins

doi:10.1128/MCB.21.21.7231-7242.2001

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Molecular and Cellular Biology, November 2001, p. 7231-7242, Vol. 21, No. 21
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7231-7242.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Ectopic Expression of DREF Induces DNA Synthesis, Apoptosis, and Unusual Morphogenesis in the Drosophila Eye Imaginal Disc: Possible Interaction with Polycomb and trithorax Group Proteins

Fumiko Hirose,¹^,^* Nobuko Ohshima,¹ Michina Shiraki,¹^, Yoshihiro H. Inoue,¹^, Osamu Taguchi,² Yoshimi Nishi,¹ Akio Matsukage,¹^,^§ and Masamitsu Yamaguchi¹

Division of Biochemistry¹ and Division of Molecular Pathology,² Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan

Received 8 March 2001/Returned for modification 25 April 2001/Accepted 6 August 2001

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 regulates DRE-containing genes. In addition,it has been reported that DREF can bind to a sequence in the hsp70scs' chromatin boundary element that is also recognized by boundaryelement-associated factor, and thus DREF may participate in regulatinginsulator activity. To examine DREF function in vivo, we establishedtransgenic flies in which ectopic expression of DREF was targetedto the eye imaginal discs. Adult flies expressing DREF exhibiteda severe rough eye phenotype. Expression of DREF induced ectopicDNA synthesis in the cells behind the morphogenetic furrow, whichare normally postmitotic, and abolished photoreceptor specificationsof R1, R6, and R7. Furthermore, DREF expression caused apoptosisin the imaginal disc cells in the region where commitment to R1/R6cells takes place, suggesting that failure of differentiationof R1/R6 photoreceptor cells might cause apoptosis. The DREF-inducedrough eye phenotype was suppressed by a half-dose reduction ofthe E2F gene, one of the genes regulated by DREF, indicating thatthe DREF overexpression phenotype is useful to screen for modifiersof DREF activity. Among Polycomb/trithorax group genes, we foundthat a half-dose reduction of some of the trithorax group genesinvolved in determining chromatin structure or chromatin remodeling(brahma, moira, and osa) significantly suppressed and that reductionof Distal-less enhanced the DREF-induced rough eye phenotype.The results suggest a possibility that DREF activity might beregulated by protein complexes that play a role in modulatingchromatin structure. Genetic crosses of transgenic flies expressingDREF to a collection of Drosophila deficiency stocks allowed usto identify several genomic regions, deletions of which causedenhancement or suppression of the DREF-induced rough eye phenotype.These deletions should be useful to identify novel targets ofDREF and its positive or negativeregulators.

^* Corresponding author. Mailing address: Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya464-8681, Japan. Phone: 81 52 762 6111, ext. 7220. Fax: 81 52763 5233. E-mail: fsegawa{at}aichi-cc.pref.aichi.jp.

Present address: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0101,Japan.

Present address: Drosophila Genetic Resource Center, Kyoto Institute of Technology, Saga, Ukyo-ku, Kyoto 616-8354,Japan.

^§ Present address: Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Bunkyo-ku, Tokyo 112-8681,Japan.

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