CDYL is a chromodomain protein that has been identified as a transcriptional co-repressor that is primarily involved in the formation of repressor complexes which coordinate histone modifications to repress gene transcription. However, most functions and mechanisms of action of the CDYL protein are unknown. In this study, we show that Cdyl-/- mice died of respiratory distress immediately at birth because of distinct abnormalities in distal lung morphogenesis which was characterized by thickened septal and expiratory alveolus atelectasis. Furthermore, Cdyl deletion in mice led to excessive proliferation of immature epithelial cells and an arrest in alveolar epithelium cell differentiation in late gestation which were associated with decreased secretion of mature surfactant proteins in alveolus. Microarray analysis showed that Cdyl gene deletion influenced the expression of genes regulating neuroactive ligand-receptor interactions, cell adhesion, and cell cycle. We validated that Cdyl repressed the transcriptional activity of Cks1 in vitro. In conclusion, Cdyl gene participates in the perinatal respiratory epithelium differentiation and maturation that is important for normal lung function at birth.
Keywords: Cdyl; Lung atelectasis; Lung epithelial differentiation; Lung morphogenesis; Transcription regulation.
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