PUBLICATION
Epigenetic regulation of cilia stability and kidney development by the chromatin remodeling SWI/SNF complex in zebrafish
- Authors
- Cheng, X., Zhu, Q., Ma, S., Peng, X., Huang, G., Liu, G., Zhang, W., Zhang, Y., Jiang, C., Qiu, A., Cao, Y.
- ID
- ZDB-PUB-251111-6
- Date
- 2025
- Source
- Journal of genetics and genomics = Yi chuan xue bao 53: 630-642 (Journal)
- Registered Authors
- Cao, Ying, Liu, Guifen
- Keywords
- Cilium, Polycystic kidney disease, SWI/SNF, Zebrafish, actl6a
- MeSH Terms
- none
- PubMed
- 41213452 Full text @ J. Genet. Genomics
Citation
Cheng, X., Zhu, Q., Ma, S., Peng, X., Huang, G., Liu, G., Zhang, W., Zhang, Y., Jiang, C., Qiu, A., Cao, Y. (2025) Epigenetic regulation of cilia stability and kidney development by the chromatin remodeling SWI/SNF complex in zebrafish. Journal of genetics and genomics = Yi chuan xue bao. 53:630-642.
Abstract
Cilia are vital subcellular organelles whose assembly is regulated by master transcription factors, such as Foxj1 and Rfx. However, the mechanisms of epigenetic regulation over cilia stability remain largely unclear. Here, we investigate the epigenetic control by manipulating chromatin remodeling genes in zebrafish. We demonstrate that the depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex induces ciliopathy-like phenotypes in zebrafish embryos. Specifically, the loss of Actl6a, an essential component of the SWI/SNF complex, leads to cilia disassembly and cystic kidney defects, without affecting cilia motility. Our multi-omics analyses (RNA-seq, ATAC-seq, and FitCUT&RUN) consistently reveal that in Actl6a-depleted pronephros or embryos, a critical set of cilia genes, including the master regulators foxj1a and rfx2, exhibit concordant downregulation across the transcriptional level, chromatin accessibility, and SWI/SNF binding. Consistently, the depletion of foxj1a or rfx2 causes cilia assembly defects and cystic kidney formation in zebrafish. Furthermore, overexpression of either foxj1a or rfx2 mRNA substantially rescues the cystic kidney and cilia disassembly defects observed in actl6a-/- mutant embryos. Collectively, these findings reveal that the SWI/SNF complex maintains cilia stability and kidney homeostasis by directly modulating the expression of the key ciliogenesis transcription factors foxj1a and rfx2.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping