SIRT6 acts as a longevity protein in rodents1,2. However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR–Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in non-human primates, and may provide mechanistic insight into human perinatal lethality syndrome.
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SIRT6 deficiency results in developmental retardation in cynomolgus monkeys, Nature, 22 August 2018
Nature, 22 August 2018
SIRT6 deficiency results in developmental retardation in cynomolgus monkeys
Weiqi Zhang, Haifeng Wan, Guihai Feng, Jing Qu, Jiaqiang Wang, Yaobin Jing, Ruotong Ren, Zunpeng Liu, Linlin Zhang, Zhiguo Chen, Shuyan Wang, Yong Zhao, Zhaoxia Wang, Yun Yuan, Qi Zhou, Wei Li*, Guang-Hui Liu* & Baoyang Hu*
Abstract
SIRT6 acts as a longevity protein in rodents1,2. However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR–Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in non-human primates, and may provide mechanistic insight into human perinatal lethality syndrome.
文章链接：https://www.nature.com/articles/s41586-018-0437-z
相关报道：https://www.nature.com/articles/d41586-018-05970-9
http://www.ibp.cas.cn/kyjz/zxdt/201808/t20180828_5059967.html