Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.
Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.
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DOI：
10.1016/j.yexcr.2016.06.013
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发表时间：
2016-08
影响因子：
3.7
通讯作者：
Kouhei Shimaji;Takahiro Konishi;H. Yoshida;H. Kimura;M. Yamaguchi
中科院分区：
文献类型：
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作者：
Kouhei Shimaji;Takahiro Konishi;H. Yoshida;H. Kimura;M. Yamaguchi
G9 a是一种在哺乳动物中发现的组蛋白H3 Lys 9（H3 K9）特异性甲基转移酶，果蝇G9 a（dG 9a）在体内可诱导H3 K9二甲基化，并在胚胎和幼虫期鉴定了dG 9a的靶基因。尽管dG 9a在多种发育过程中很重要，但dG 9a与信号通路之间的联系尚未得到解决。在这里，通过全基因组遗传筛选，利用在眼盘中过表达dG 9a的果蝇的粗糙眼表型，我们鉴定了16个增强dG 9a过表达诱导的粗糙眼表型的基因。这16个基因包括表皮生长因子受体（EGFR）信号通路的组成部分Star、前开、BereftandF-box和富亮氨酸重复序列蛋白6。当G9 a过表达与Star突变结合时，眼内成虫盘R7光感受器以及蛹视网膜视锥细胞和色素细胞的分化受到严重抑制。此外，dG 9a过表达降低了眼盘中激活的ERK信号。这些数据表明G9 a和EGFR信号通路之间存在密切的遗传联系。
G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals.DrosophilaG9a (dG9a) has been reported to induce H3K9 dimethylationin vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet. Here, by genome-wide genetic screen, taking advantage of the rough eye phenotype of flies that over-express dG9a in eye discs, we identified 16 genes that enhanced the rough eye phenotype induced bydG9aover-expression. These 16 genes includedStar, anterior open, bereftandF-box and leucine-rich repeat protein 6which are components of epidermal growth factor receptor (EGFR) signaling pathway. WhendG9aover-expression was combined with mutation ofStar, differentiation of R7 photoreceptors in eye imaginal discs as well as cone cells and pigment cells in pupal retinae was severely inhibited. Furthermore, thedG9aover-expression reduced the activated ERK signals in eye discs. These data demonstrate a strong genetic link betweendG9aand the EGFR signaling pathway.