FOXJ1 transcriptional targets in human airway cells and impaired multiciliogenesis in <i>FOXJ1</i> -associated primary ciliary dyskinesia

Abstract Fluid mobilization on epithelia is ensured by the motile cilia of differentiated multiciliated cells (MCCs). Key transcriptional regulators of motile ciliogenesis include CCNO, MCIDAS, RFXs, and the transcription factor FOXJ1, whose precise role in humans remains unclear. We show that, unlike CCNO and MCIDAS, FOXJ1 expression persists in well-differentiated human airway epithelial cells (hAECs), suggesting functions beyond cilia initiation. ChIP-seq in hAECs allowed us to refine the consensus target motifs of FOXJ1 and RFXs, as well as their close proximity, which strongly suggests functional cooperation within a transcriptional complex. By combining ChIP-seq in normal cells with RNAseq from patients with FOXJ1-related primary ciliary dyskinesia (PCD), we identified 683 direct FOXJ1 target genes. Among these, 89 MCC-enriched genes—particularly those encoding axonemal proteins such as microtubule-inner proteins (MIPs) and dynein arm docking components—were downregulated in FOXJ1-deficient cells. Collectively, these findings provide new insights into how FOXJ1 contributes to human motile ciliogenesis, and reveal a potential role for FOXJ1 in maintaining MCCs differentiation and ciliary function by sustaining the expression of ciliary proteins, particularly those in direct contact with axonemal tubulin.