Differential activity of EWG transcription factor isoforms identifies a subset of differentially regulated genes important for synaptic growth regulation
Differential activity of EWG transcription factor isoforms identifies a subset of differentially regulated genes important for synaptic growth regulation
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DOI：
10.1016/j.ydbio.2010.09.006
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发表时间：
2010-12-15
影响因子：
2.7
通讯作者：
Soller, Matthias
中科院分区：
文献类型：
--
作者：
Haussmann, Irmgard U.;Soller, Matthias
人类基因组中的绝大多数基因都是选择性剪接这种类型的转录后基因调控的功能后果在大脑中特别突出，但在很大程度上仍然难以捉摸在这里，我们分析了选择性剪接在果蝇转录因子直立翼（ewg）中的作用，并通过编码不同异构体的转基因的差异拯救来剖析其功能完全表达SC3 ORF异构体的转基因 相比之下，表达缺乏外显子 D 和 J 的 Delta DJ 亚型的转基因具有较低的活性（从其表达水平推断），并且对活力和突触生长缺陷的拯救作用减弱。 SO 同工型 这些基因主要参与调节基因表达，而 EWG 的核心功能是通过两种同工型对代谢基因的调节来表明的。 总之，我们证明了转录因子 EWG 的不同同工型编码转基因的差异拯救鉴定了一组与突触生长调节相关的独特基因 (C) 2010 Elsevier Inc 保留所有权利
The vast majority of genes in the human genome is alternatively spliced The functional consequences of this type of post transcriptional gene regulation that is particularly prominent in the brain however remains largely elusive Here we analyzed the role of alternative splicing in the transcription factor erect wing (ewg) in Drosophila and dissect its function through differential rescue with transgenes encoding different isoforms Transgenes expressing the SC3 ORF isoform fully rescue viability and synaptic growth defects In contrast transgenes expressing the Delta DJ isoform that lack exons D and J have a lower activity as inferred from their expression levels and exert reduced rescue of viability and synaptic growth defects By comparison of the gene expression profile of ewe mutants rescued either by the SC3 ORF or the Delta DJ transgene we identified a set of genes whose expression is exclusively restored by the SO isoform These genes are mostly Involved in regulating gene expression while a core function of EWG is indicated by the regulation of metabolic genes by both isoforms In conclusion we demonstrated that differential rescue with different isoform encoding transgenes of the transcription factor EWG identifies a unique set of genes associated with synaptic growth regulation (C) 2010 Elsevier Inc All rights reserved