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首页> 外文期刊>Molecular and Cellular Biology >Ectopic Expression of DREF Induces DNA Synthesis, Apoptosis, and Unusual Morphogenesis in the Drosophila Eye Imaginal Disc: Possible Interaction with Polycomband trithorax Group Proteins
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Ectopic Expression of DREF Induces DNA Synthesis, Apoptosis, and Unusual Morphogenesis in the Drosophila Eye Imaginal Disc: Possible Interaction with Polycomband trithorax Group Proteins

机译：DREF异位表达诱导果蝇眼想象盘中的DNA合成，细胞凋亡和异常形态发生：可能与Polycomband trithorax组蛋白相互作用。

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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-lessenhanced 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 ofDrosophila 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.
机译：编码DNA复制相关蛋白的果蝇基因的启动子除E2F识别位点外，还包含转录调控元件DRE（5'-TATCGATA）。特定的DRE结合因子DREF正调控含DRE的基因。另外，据报道，DREF可以与 hsp70 scs'染色质边界元件中的序列结合，该序列也被边界元素相关因子识别，因此DREF可以参与调节绝缘子的活性。为了检查DREF在体内的功能，我们建立了转基因果蝇，其中DREF的异位表达靶向于眼部视盘。表达DREF的成年蝇表现出严重的粗糙眼表型。 DREF的表达在形态发生犁沟后的细胞中诱导异位DNA合成，而这种发育通常是有丝分裂后的，并且废除了R1，R6和R7的感光受体规格。此外，DREF表达引起对R1 / R6细胞的承诺发生区域的椎间盘细胞凋亡，提示R1 / R6感光细胞的分化失败可能导致凋亡。 DREF调控的基因之一 E2F 基因的半剂量减少抑制了DREF诱导的粗糙眼表型，表明DREF过表达表型可用于筛选DREF活性修饰因子。在 Polycomb / trithorax 组基因中，我们发现某些 trithorax 组基因参与确定染色质结构或染色质重塑（ brahma < / em>， moira 和 osa ）被显着抑制，而 Distal-less 的减少增强了DREF诱导的粗糙眼表型。结果表明，DREF活性可能受蛋白复合物调节，而蛋白复合物在调节染色质结构中起作用。表达DREF的果蝇缺乏果蝇种群的DREF转基因果蝇的遗传杂交使我们能够鉴定出几个基因组区域，这些区域的缺失引起DREF诱导的粗糙眼表型的增强或抑制。这些删除将有助于确定DREF及其正或负调节剂的新靶标。

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