Silica nanoparticle releases SIRT6-induced epigenetic silencing of follistatin.

Silica nanoparticle releases SIRT6-induced epigenetic silencing of follistatin.
复制标题

二氧化硅纳米颗粒释放 SIRT6 诱导的卵泡抑素表观遗传沉默。

DOI:
10.1016/j.biocel.2017.12.011
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发表时间:
2018-02
期刊:
Int J Biochem Cell Biol.
影响因子:
--
通讯作者:
Gao Xiangwei
Gao Xiangwei
中科院分区:
其他
文献类型:
--
作者:
Zhang Lingda;Han Bing;Xiang Jie;Liu Kangli;Dong Haojie;Gao Xiangwei

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卵泡抑素(FST)在二氧化硅纳米颗粒(SiO2 NP)暴露期间起保护作用。SiO2 NP处理诱导FST转录,其机制未知。我们在此报道了sirtuin家族成员之一SIRT 6诱导FST的表观遗传沉默。SIRT 6基因敲低后FST的表达升高,而SIRT 6基因过表达后FST的表达降低。染色质免疫沉淀显示SIRT 6与FST启动子之间存在直接相互作用。SIRT 6的敲低增加了FST启动子区Ac-H3 K9和Ac-H3 K56的水平。SiO2 NP处理使SIRT 6 mRNA失稳并降低SIRT 6表达,导致FST转录激活。最后,SIRT 6的过表达增加SiO2 NP诱导的细胞凋亡。总的来说,这项研究提供的证据表明,SIRT 6是FST转录的负调节因子,并参与二氧化硅纳米颗粒暴露期间细胞存活的调节。
Follistatin (FST) plays a protective role during silica nanoparticle (SiO2NP) exposure. SiO2NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST. The expression of FST was elevated after SIRT6 knockdown while reduced after SIRT6 overexpression. Chromatin immunoprecipitation revealed a direct interaction between SIRT6 with FST promoter. Knockdown of SIRT6 increased both Ac-H3K9 level and Ac-H3K56 level at FST promoter region. SiO2NP treatment de-stabilized SIRT6 mRNA and reduced SIRT6 expression, leading to the activation of FST transcription. Finally, over-expression of SIRT6 increased SiO2NP-induced apoptosis. Collectively, this study provided evidence that SIRT6 is a negative regulator of FST transcription and participates in the regulation of cell survival during silica nanoparticle exposure.
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