| First Author | Liu X | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 9 | Pages | 101461 |
| PubMed ID | 32861997 | Mgi Jnum | J:306820 |
| Mgi Id | MGI:6717608 | Doi | 10.1016/j.isci.2020.101461 |
| Citation | Liu X, et al. (2020) SIRT7 Facilitates CENP-A Nucleosome Assembly and Suppresses Intestinal Tumorigenesis. iScience 23(9):101461 |
| abstractText | SIRT7 is a member of the mammalian sirtuins and functions as an NAD(+)-dependent deacylase. Here we show that SIRT7 deficiency leads to a lowered histone acetyltransferase 1 (HAT1) activity and therefore decreased histone H4K5 and H4K12 acetylation. This in turn causes CENP-A dislocation at the centromere, which further affects chromatin assembly. SIRT7 ablation results in aneuploidy and aging phenotypes, including senescence and nucleolar expansion. Moreover, SIRT7 knockout mice are susceptible to DSS-induced colitis and alcohol-derived epithelial disturbance, revealing a disrupted intestinal epithelial homeostasis. Notably, absence of SIRT7 aggravates the susceptibility of colorectal cancer incidence in APC(Min/+) mouse model and elicits further the Wnt signaling. Our findings indicate a tumor suppressive role of SIRT7 in the case of colorectal cancer. Together with the activities in maintaining genome integrity and intestinal homeostasis, activating SIRT7 may serve as a strategy to treat bowel diseases and colorectal cancer. |
