SIRT7 Facilitates CENP-A Nucleosome Assembly and Suppresses Intestinal Tumorigenesis.

ABSTRACT: 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 si

SUBMITTER: Liu X 

PROVIDER: S-EPMC7476862 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature