Asymmetrical arginine dimethylation of histone H4 by 8-oxog/OGG1/PRMT1 is essential for oxidative stress-induced transcription activation
Asymmetrical arginine dimethylation of histone H4 by 8-oxog/OGG1/PRMT1 is essential for oxidative stress-induced transcription activation
复制标题
8-oxog/OGG1/PRMT1 对组蛋白 H4 的不对称精氨酸二甲基化对于氧化应激诱导的转录激活至关重要
DOI：
10.1016/j.freeradbiomed.2020.12.457
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发表时间：
2021-01-17
影响因子：
7.4
通讯作者：
Guo, Zhigang
中科院分区：
文献类型：
--
作者：
Wang, Wentao;Ma, Ying;Guo, Zhigang
已经确定8-氧代鸟嘌呤DNA糖基化酶1（OGG 1）是在氧化应激下去除氧化鸟嘌呤的主要酶。然而，越来越多的证据表明，OGG 1不仅是一个碱基切除修复蛋白，而且是一个新的转录辅激活因子，参与氧化应激诱导的基因表达。其下游靶基因和潜在的调控机制仍需进一步研究。在此，发现c-Myc是OGG 1在氧化应激下的下游靶标，并且H4 R3 me 2a参与该转录调节。H2 O2诱导的H4 R3 me 2a水平升高受OGG 1调节，OGG 1可能直接与特异性精氨酸甲基转移酶PRMT 1相互作用，促进H4 R3 me 1的不对称二甲基化。在c-Myc启动子上富集H4 R3 me 2a可以募集YY 1并激活c-Myc转录。此外，敲低OGG 1或PRMT 1通过下调H4 R3 me 2a的形成来抑制c-Myc在氧化应激下的转录。此外，野生型（WT）H4 R3的过表达促进c-Myc转录，但突变型H4 R3 Q的表达不具有这种作用。综上所述，我们的数据表明，8-oxoG/OGG 1/PRMT 1/H4 R3 me 2a/YY 1轴感知氧化应激并促进基因转录。
It has been established that 8-oxoguanine DNA glycosylase 1 (OGG1) is the main enzyme removing oxidized guanine under oxidative stress. However, increasing evidence has shown that OGG1 is not only a base excision repair protein but also a new transcriptional coactivator involved in oxidative stress-induced gene expression. Its downstream target genes and the underlying regulatory mechanisms still need to be discerned. Here, it was discovered that c-Myc is a downstream target of OGG1 under oxidative stress and that H4R3me2a is involved in this transcriptional regulation. The increased level of H4R3me2a induced by H2O2 is regulated by OGG1, which may directly interact with the specific arginine methyltransferase PRMT1 and promote the asymmetrical dimethylation of H4R3me1. H4R3me2a enrichment on the promoter of c-Myc can recruit YY1 and activate c-Myc transcription. Moreover, knocking down OGG1 or PRMT1 suppresses c-Myc transcription under oxidative stress by downregulating H4R3me2a formation. Furthermore, the overexpression of wild type (WT) H4R3 promotes c-Myc transcription, but the expression of mutant H4R3Q does not have this effect. Taken together, our data show that the 8-oxoG/OGG1/PRMT1/H4R3me2a/YY1 axis senses oxidative stress and promotes gene transcription.