Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage.

Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage.
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果蝇 UTX 与 p53 协调调节 ku80 表达以应对 DNA 损伤

DOI:
10.1371/journal.pone.0078652
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Fang M
Fang M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang C;Hong Z;Ma W;Ma D;Qian Y;Xie W;Tie F;Fang M

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UTX被认为是发育过程中激活基因转录的一般因子。在这里,我们证明了一个额外的重要作用UTX的DNA损伤反应,其中它上调表达ku80果蝇,无论是在培养的细胞和三龄幼虫。我们进一步表明,UTX介导的表达ku80的H3K27me3在ku80启动子的去甲基化后暴露于电离辐射(IR)在p53依赖性的方式。UTX与p53物理相互作用,并且UTX和p53在IR暴露后以相互依赖的方式被募集到ku80启动子。而UTX的缺失对ku70、mre 11、hid和reaper的表达影响不大,提示UTX对ku80的表达具有特异性调控作用。因此,我们的研究结果进一步阐明了UTX的分子功能。
UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.
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