Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents.
Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents.
复制标题
Dicer 与 SIRT7 相互作用并调节 H3K18 脱乙酰化以响应 DNA 损伤剂
DOI：
10.1093/nar/gkv1504
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发表时间：
2016-05-05
影响因子：
14.9
通讯作者：
Tang KF
中科院分区：
文献类型：
--
作者：
Zhang PY;Li G;Deng ZJ;Liu LY;Chen L;Tang JZ;Wang YQ;Cao ST;Fang YX;Wen F;Xu Y;Chen X;Shi KQ;Li WF;Xie C;Tang KF
Dicer参与裂殖酵母和植物中异染色质的形成。然而，它是否在哺乳动物中具有类似的作用仍然存在争议。在这里，我们表明，人类Dicer蛋白与SIRT7相互作用，SIRT7是一种NAD+依赖性H3K18Ac（组蛋白H3的乙酰化赖氨酸18）脱乙酰酶，并在细胞质中保持一定比例的SIRT7。Dicer敲低导致染色质相关SIRT7的增加，同时细胞质SIRT7的减少，而其过表达诱导SIRT7在染色质相关组分中的减少和在细胞质中的增加。此外，DNA损伤剂促进Dicer表达，导致染色质相关SIRT7水平降低和H3K18Ac水平增加，这可以通过Dicer敲低来缓解。结合H3K18Ac仅与染色质相关，我们的研究结果表明，DNA损伤处理的Dicer诱导可能通过在细胞质中捕获更多SIRT7来防止H3K18Ac脱乙酰化。
Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD+-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.