PUBLICATION
Identification and functional study of enhancers of EYA1, the causative gene of branchio-oto-renal syndrome
- Authors
- Wang, F., Zhang, R., Jian, J., Sun, Y., Li, Q.
- ID
- ZDB-PUB-240117-2
- Date
- 2024
- Source
- Developmental neuroscience 46(5): 333-340 (Journal)
- Registered Authors
- Li, Qiang
- Keywords
- none
- MeSH Terms
-
- Animals
- Branchio-Oto-Renal Syndrome*/genetics
- Enhancer Elements, Genetic*/genetics
- Humans
- Protein Tyrosine Phosphatases*/genetics
- Protein Tyrosine Phosphatases*/metabolism
- Intracellular Signaling Peptides and Proteins*/genetics
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism
- Zebrafish
- PubMed
- 38228108 Full text @ Dev. Neurosci.
Citation
Wang, F., Zhang, R., Jian, J., Sun, Y., Li, Q. (2024) Identification and functional study of enhancers of EYA1, the causative gene of branchio-oto-renal syndrome. Developmental neuroscience. 46(5):333-340.
Abstract
Introduction Branchio-oto-renal syndrome (BOR syndrome) is a rare genetic disorder with an incidence of 1 in 40,000, affecting the development of multiple organs, including the branchio, ear and kidney. It is responsible for 2% of childhood deafness. Currently, variants in the coding regions of the main causative genes, such as EYA1, SIX1, and SIX5, explain only half of the disease's etiology. Therefore, there is a need to explore the non-coding regions, which constitute the majority of the genome, especially the regulatory regions, as potential new causative factors.
Method In this study, we focused on the EYA1 gene, which accounts for over 40% of BOR syndrome cases, and conducted a screening of candidate enhancers within a 250 kb region upstream and downstream of the gene using comparative genomics. We characterized the enhancer activities of these candidates in zebrafish using the Tol2 transposon system.
Results Our findings revealed that out of the 11 conserved non-coding elements (CNEs) examined, four exhibited enhancer activity. Notably, CNE16.39 and CNE16.45 displayed tissue-specific enhancer activity in the ear. CNE16.39required the full-length 206 bp sequence for inner-ear-specific expression, while the core functional region of CNE16.45 was identified as 136 bp. Confocal microscopy results demonstrated that both CNE16.39 and CNE16.45 drove the expression of GFP in the sensory region of the crista of the inner ear in zebrafish, consistent with the expression pattern of eya1.
Conclusion This study contributes to the understanding of the regulatory network governing EYA1 expression and offers new insights to further clarify the pathogenic role of EYA1 in BOR syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping