Epigenetic regulation of cilia stability and kidney development by the chromatin remodeling SWI/SNF complexes [FitCUT&RUN]

Cilia are important subcellular organelles and are regulated by transcription factors including Foxj1 and Rfx proteins. Whether and how are cilia regulated at epigenetic level remains unknown. We addressed this question by knocking down or knocking out of chromatin remodeling genes. Interestingly, depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) complexes lead to ciliopathy-like phenotypes in zebrafish embryos. Specifically, depletion of Actl6a, one of the components of the SWI/SNF complexes lead cilia disassembly and cystic kidney, but do not affect cilia motility. Omics studies show that in Actl6a-depleted embryos, a set of cilia genes including Foxj1a and Rfx2, the master regulators of cilia assembly, were downregulated at transcriptional level, chromatin accessibility and the SWI/SNF complexes binding. Thus, our study reveals that the SWI/SNF complexes regulate cilia stability and kidney development by direct modulating the expression Foxj1a and Rfx2. Overall design: To detect changes in the binding of SWI/SNF complexes in the genome after actl6a knockdown, we used Fit-Cleavage Under Targets & Release Using Nuclease (FitCUT&RUN) for smarca4a in actl6a morphant.