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SIRT7 Facilitates CENP-A Nucleosome Assembly and Suppresses Intestinal Tumorigenesis
- Source :
- iScience, Vol 23, Iss 9, Pp 101461- (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Summary: 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 APCMin/+ 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.
- Subjects :
- Molecular Biology
Molecular Genetics
Cancer
Science
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 23
- Issue :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f72338b9b38f4f6fa052eb142ae3064f
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2020.101461