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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,dagger Yoshihiro H. Inoue,1,Dagger 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 hsp70 scs' chromatin boundary element that is also recognized by boundary element-associated factor, and thus DREF may participate in regulating insulator activity. To examine DREF function in vivo, we established transgenic flies in which ectopic expression of DREF was targeted to the eye imaginal discs. Adult flies expressing DREF exhibited a severe rough eye phenotype. Expression of DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow, which are normally postmitotic, and abolished photoreceptor specifications of R1, R6, and R7. Furthermore, DREF expression caused apoptosis in the imaginal disc cells in the region where commitment to R1/R6 cells takes place, suggesting that failure of differentiation of R1/R6 photoreceptor cells might cause apoptosis. The DREF-induced rough eye phenotype was suppressed by a half-dose reduction of the E2F gene, one of the genes regulated by DREF, indicating that the DREF overexpression phenotype is useful to screen for modifiers of DREF activity. Among Polycomb/trithorax group genes, we found that a half-dose reduction of some of the trithorax group genes involved in determining chromatin structure or chromatin remodeling (brahma, moira, and osa) significantly suppressed and that reduction of Distal-less enhanced the DREF-induced rough eye phenotype. The results suggest a possibility that DREF activity might be regulated by protein complexes that play a role in modulating chromatin structure. Genetic crosses of transgenic flies expressing DREF to a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or suppression of the DREF-induced rough eye phenotype. These deletions should be useful to identify novel targets of DREF and its positive or negative regulators.

* Corresponding author. Mailing address: Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan. Phone: 81 52 762 6111, ext. 7220. Fax: 81 52 763 5233. E-mail: fsegawa{at}aichi-cc.pref.aichi.jp.

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

Dagger 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.

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.


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