Shijia Bi, Xiaoyu Jiang, Qianzhao Ji, Zehua Wang, Jie Ren, Si Wang, Yang Yu, Ruoqi Wang, Zunpeng Liu, Junhang Liu, Jianli Hu, Guoqiang Sun, Zeming Wu, Zhiqing Diao, Jingyi Li, Liang Sun, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Guang-Hui Liu, Jing Qu
Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops...
March 11, 2024: Developmental Cell