PUBLICATION
Disruption of sirtuin 7 in zebrafish facilitates hypoxia tolerance
- Authors
- Liao, Q., Zhu, C., Sun, X., Wang, Z., Chen, X., Deng, H., Tang, J., Jia, S., Liu, W., Xiao, W., Liu, X.
- ID
- ZDB-PUB-230723-48
- Date
- 2023
- Source
- The Journal of biological chemistry 299(8): 105074 (Journal)
- Registered Authors
- Xiao, Wuhan
- Keywords
- gene expression, hif-1αa, hif-1αb, hif-2αa, hif-2αb, hypoxia signaling, sirt7
- MeSH Terms
-
- Anaerobiosis
- Animals
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Oxygen*/metabolism
- Proteolysis
- Sirtuins*/genetics
- Sirtuins*/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 37481210 Full text @ J. Biol. Chem.
Citation
Liao, Q., Zhu, C., Sun, X., Wang, Z., Chen, X., Deng, H., Tang, J., Jia, S., Liu, W., Xiao, W., Liu, X. (2023) Disruption of sirtuin 7 in zebrafish facilitates hypoxia tolerance. The Journal of biological chemistry. 299(8):105074.
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 addition, sirt7 not only binds to the hypoxia responsive element (HRE) of hypoxia-inducible gene promoters, but also causes a reduction of H3K18Ac on these promoters. Sirt7 may regulate hypoxia-responsive gene expression through its enzymatic and non-enzymatic activities. This study provides novel insights into sirt7 function and sheds new lights on the regulation of hypoxia signaling by sirt7.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping