Characterization of Drosophila G9a in vivo and identification of genetic interactants
Characterization of Drosophila G9a in vivo and identification of genetic interactants
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DOI：
10.1111/j.1365-2443.2008.01199.x
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发表时间：
2008-07-01
期刊：
影响因子：
2.1
通讯作者：
Yamaguchi, Masamitsu
中科院分区：
文献类型：
--
作者：
Kato, Yasuko;Kato, Masaki;Yamaguchi, Masamitsu
在哺乳动物中，G9a是一种组蛋白H3赖氨酸9 （H3- k9）特异性组蛋白甲基转移酶（HMTase），已知对小鼠胚胎发生至关重要。有报道称果蝇G9a （dG9a）是斑点位置效应的显性抑制因子，在体外具有HMTase活性，对果蝇发育具有重要意义。我们发现dG9a在体内具有H3-K9二甲基化活性，对HP1在常染色质区域的募集很重要。尽管甲基化酶缺陷突变体没有表现出这种影响，但在眼成像盘中的过度表达抑制了蛹胚轴细胞的分化，并导致成虫的眼睛形态异常（粗糙的眼睛表型）。这些结果表明dG9a的HMTase活性影响蛹眼形成相关基因的转录。Polycomb group （PcG）基因减少一半剂量可增强dg9a诱导的粗糙眼表型。相比之下，编码组蛋白H3-K4去甲基化酶的小想象盘（lid）突变体显示dG9a诱导的粗糙眼表型受到抑制。此外，眼睑在眼影像盘中的共表达增强了dG9a诱导的粗糙表型。结果表明，dG9a的功能在体内受到PcG复合物的负调控，而受到Lid的正调控。
In mammals, G9a is a histone H3 lysine 9 (H3-K9)-specific histone methyltransferase (HMTase), known to be essential for murine embryogenesis. It has been reported that Drosophila G9a (dG9a) is a dominant suppressor of position effects of variegation, has HMTase activity in vitro, and is important for Drosophila development. Here we show that dG9a has H3-K9 dimethylation activity in vivo and is important for the recruitment of HP1 in the euchromatic region. Over-expression in eye imaginal discs inhibited the differentiation of pupal ommatidial cells and resulted in abnormal eye morphology (rough eye phenotype) in the adults, although a methylase defective mutant did not demonstrate such effects. These results suggest that HMTase activity of dG9a affects transcription of genes involved in pupal eye formation.The dG9a-induced rough eye phenotype was enhanced by a half-dose reduction of the Polycomb group (PcG) gene. In contrast, mutants for little imaginal discs (lid), encoding histone H3-K4 demethylase, demonstrated suppression of the rough eye phenotype induced by dG9a. Furthermore co-expression of Lid in eye imaginal discs enhanced the rough phenotype induced by dG9a. The results suggest that the function of dG9a is negatively regulated by the PcG complex and positively regulated by Lid in vivo.