| Literature DB >> 30135584 |
Weiqi Zhang1,2,3,4, Haifeng Wan2,3,4, Guihai Feng2,3,4, Jing Qu2,3,4, Jiaqiang Wang2,3,4, Yaobin Jing1,3, Ruotong Ren1,3,4, Zunpeng Liu2,3, Linlin Zhang2,3, Zhiguo Chen5, Shuyan Wang5, Yong Zhao6, Zhaoxia Wang7, Yun Yuan7, Qi Zhou2,3,4, Wei Li8,9,10, Guang-Hui Liu11,12,13,14, Baoyang Hu15,16,17.
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.Entities:
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Year: 2018 PMID： 30135584 DOI： 10.1038/s41586-018-0437-z
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962