The histone H3 acetylase dGcn5 is a key player in Drosophila melanogaster metamorphosis
The histone H3 acetylase dGcn5 is a key player in Drosophila melanogaster metamorphosis
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DOI：
10.1128/mcb.25.18.8228-8238.2005
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发表时间：
2005-09-01
影响因子：
5.3
通讯作者：
Antoniewski, C
中科院分区：
文献类型：
--
作者：
Carré, C;Szymczak, D;Antoniewski, C
虽然组蛋白乙酰转移酶（HATs）参与了染色质结构和基因转录的调节，但关于其在高等生物中的发育作用的研究却很少。Gen5是在真核生物中发现的第一个具有HAT活性的转录因子。在这里，我们报告的果蝇dGcn5突变体的分离和表征。dGcn5等位基因阻断了卵子发生和变态的发生，而亚型dGcn5等位基因损害了成体附属物和角质层的形成。引人注目的是，在dGcn 5突变体中组蛋白H3的K9和K14赖氨酸残基的乙酰化的急剧损失对幼虫组织没有明显的影响。相比之下，观察到在成虫组织中的强细胞增殖缺陷。体内互补实验表明，dGcn5除了染色体结合和乙酰化之外还整合了特定的功能。令人惊讶的是，具有布罗莫结构域缺失的dGcn5变体蛋白，其已显示识别乙酰化组蛋白，似乎是完全功能性的。我们的研究结果建立dGcn5作为一个主要的组蛋白H3乙酰化酶在果蝇的发育过渡过程中起着关键作用，在特定的形态发生级联控制。
Although it has been well established that histone acetyltransferases (HATs) are involved in the modulation of chromatin structure and gene transcription, there is only little information on their developmental role in higher organisms. Gen5 was the first transcription factor with HAT activity identified in eukaryotes. Here we report the isolation and characterization of Drosophila melanogaster dGcn5 mutants. Null dGcn5 alleles block the onset of both oogenesis and metamorphosis, while hypomorphic dGcn5 alleles impair the formation of adult appendages and cuticle. Strikingly, the dramatic loss of acetylation of the K9 and K14 lysine residues of histone H3 in dGcn5 mutants has no noticeable effect on larval tissues. In contrast, strong cell proliferation defects in imaginal tissues are observed. In vivo complementation experiments revealed that dGcn5 integrates specific functions in addition to chromosome binding and acetylation. Surprisingly, a dGcn5 variant protein with a deletion of the bromodomain, which has been shown to recognize acetylated histones, appears to be fully functional. Our results establish dGcn5 as a major histone H3 acetylase in Drosophild which plays a key role in the control of specific morphogenetic cascades during developmental transitions.