In budding tunicates, aging accompanies a decrease in the gene expression of mitochondrial transcription factor A (Tfam), and the in vivo transfection of Tfam mRNA stimulates the mitochondrial respiratory activity of aged animals. The gene expression of both the transcriptional repressor Yin-Yang-1 (YY1) and corepressor Sirtuin6 (Sirt6) increased during aging, and the co-transfection of synthetic mRNA of YY1 and Sirt6 synergistically down-regulated Tfam gene expression. Pull-down assays of proteins indicated that YY1-associated factor 2 (YAF2) was associated with both YY1 and SIRT6. Protein cross-linking confirmed that YAF2 bound YY1 and SIRT6 with a molar ratio of 1:1. YY1 was bound to CCAT- or ACAT-containing oligonucleotides in the 5′ flanking region of the Tfam gene. ChIP-qPCR showed that SIRT6 specifically induced the histone H3K9 deacetylation of the Tfam upstream region. YY1 and YAF2 accelerated SIRT6-induced H3K9 deacetylation. YY1 and Sirt6 mRNA transfection attenuated mitochondrial respiratory gene expression and blocked MitoTracker fluorescence. In contrast, the SIRT6 inhibitor and Tfam mRNA antagonized the inhibitory effects of YY1 and Sirt6, indicating that Tfam acts on mitochondria downstream of YY1 and Sirt6. We concluded that in the budding tunicate, Polyandrocarpa misakiensis, YY1 recruits SIRT6 via YAF2 to the TFAM gene, resulting in aging-related mitochondrial down-regulation.

中文翻译：

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YAF2介导的YY1-Sirtuin6相互作用负责衰老被囊动物的线粒体下调

在萌芽的被囊类动物中，衰老伴​​随着线粒体转录因子 A ( Tfam )基因表达的降低，Tfam mRNA 的体内转染刺激了衰老动物的线粒体呼吸活动。转录抑制因子Yin-Yang-1 ( YY1 ) 和辅助抑制因子Sirtuin6 ( Sirt6 )的基因表达在衰老过程中增加，YY1和Sirt6合成mRNA 的共转染协同下调Tfam基因表达。蛋白质的下拉分析表明 YY1 相关因子 2 (YAF2) 与 YY1 和 SIRT6 都相关。蛋白质交联证实 YAF2 以 1:1 的摩尔比结合 YY1 和 SIRT6。YY1 与Tfam基因5' 侧翼区域中含有 CCAT 或 ACAT 的寡核苷酸结合。ChIP-qPCR 显示 SIRT6 特异性诱导Tfam上游区域的组蛋白 H3K9 去乙酰化。YY1 和 YAF2 加速了 SIRT6 诱导的 H3K9 去乙酰化。YY1和Sirt6 mRNA 转染减弱了线粒体呼吸基因的表达并阻断了 MitoTracker 荧光。相反，SIRT6抑制剂和Tfam mRNA拮抗YY1的抑制作用和Sirt6，表明Tfam作用于YY1和Sirt6下游的线粒体。我们的结论是，在萌芽被囊动物，Polyandrocarpa misakiensis，YY1通过YAF2新兵SIRT6的TFAM基因，从而导致衰老相关的线粒体下调。