Follistatin (FST) plays a protective role during silica nanoparticle (SiO NP) exposure. SiO NP 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. SiO NP treatment de-stabilized SIRT6 mRNA and reduced SIRT6 expression, leading to the activation of FST transcription. Finally, over-expression of SIRT6 increased SiO NP-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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