Disruption of sirtuin 7 in zebrafish facilitates hypoxia tolerance.

ABSTRACT: SIRT7 is a member of the sirtuin family proteins with nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylase activity, which can inhibit the activity of hypoxia-inducible factors independently of its enzymatic activity. However, the role of SIRT7 in affecting hypoxia signaling in vivo is still elusive. Here, we find that sirt7-null zebrafish are more resistant to hypoxic conditions, along with an increase of hypoxia-responsive gene expression and erythrocyte numbers, compared with their wildtype siblings. Overexpression of sirt7 suppresses the expression of hypoxia-responsive genes. Further assays indicate that sirt7 interacts with zebrafish hif-1αa, hif-1αb, hif-2αa, and hif-2αb to inhibit their transcriptional activity and mediate their protein degradation. In

SUBMITTER: Liao Q 

PROVIDER: S-EPMC10448219 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature