PUBLICATION
Zebrafish optineurin: genomic organization and transcription regulation
- Authors
- Silva, I.A.L., Varela, D., Cancela, M.L., Conceição, N.
- ID
- ZDB-PUB-220831-13
- Date
- 2022
- Source
- Genome 65(10): 513-523 (Journal)
- Registered Authors
- Cancela, Leonor
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Cycle Proteins*/genetics
- Cell Cycle Proteins*/metabolism
- Genomics
- Humans
- Membrane Transport Proteins*/genetics
- Membrane Transport Proteins*/metabolism
- NF-kappa B*/genetics
- NF-kappa B*/metabolism
- Signal Transduction
- Transcription Factor TFIIIA*/genetics
- Transcription Factor TFIIIA*/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 36037528 Full text @ Genome
Citation
Silva, I.A.L., Varela, D., Cancela, M.L., Conceição, N. (2022) Zebrafish optineurin: genomic organization and transcription regulation. Genome. 65(10):513-523.
Abstract
Optineurin (OPTN) is involved in a variety of mechanisms such as autophagy, vesicle trafficking, and NF-κB signaling. Mutations in the OPTN gene have been associated with different pathologies including glaucoma, amyotrophic lateral sclerosis and Paget's disease of bone. Since the relationship between fish and mammalian OPTN is not well understood the objective of the present work was to characterize the zebrafish optn gene and protein structure and to investigate its transcriptional regulation. Through a comparative in silico analysis, we observed that zebrafish optn presents genomic features similar to those of its human counterpart, including its neighboring genes and structure. A comparison of OPTN protein from different species revealed a high degree of conservation in its functional domains and 3D structure. Furthermore, our in vitro transient-reporter analysis identified a functional promoter in the upstream region of the zebrafish optn gene, along with a region important for its transcription regulation. Site-directed mutagenesis revealed that the NF-κB motif is responsible for the activation of this region. In conclusion, with this study, we characterize zebrafish optn and our results indicate that zebrafish can be considered as an alternative model to study OPTN's biological role in bone-related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping