Zebrafish optineurin: genomic organization and transcription regulation

Optineurin (OPTN) is involved in a variety of mechanisms, such as autophagy, vesicle trafficking, and nuclear factor kappa-B (NF-kappa B) signaling. Mutations in the OPTN gene have been associated with different pathologies, including glaucoma, amy-otrophic 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 in-vestigate 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 three-dimensional 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-kappa B 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.

Automated summary

This study characterized the zebrafish optn gene and protein structure and investigated its transcriptional regulation. Comparative analysis revealed similarities between zebrafish and human OPTN in genomic features, neighboring genes, and structure. Conservation of functional domains and three-dimensional structure of OPTN protein was observed across different species. In vitro experiments identified a functional promoter and a region important for transcriptional regulation in the zebrafish optn gene.