Depletion of PHF14, a novel histone-binding protein gene, causes neonatal lethality in mice due to respiratory failure.

The plant homeodomain (PHD) finger is identified in many chromatin-binding proteins, and functions as a 'reader' that recognizes specific epigenetic marks on histone tails, bridging transcription factors and their associated complexes to chromatin, and regulating gene expression. PHD finger-containing proteins perform many biological functions and are involved in many human diseases including cancer. PHF14 is predicted to code for a protein with multiple PHD fingers. However, its function is unidentified. The aim of this study is to characterize PHF14 and investigate its biological significance by employing multiple approaches including mouse gene-targeting knockout, and molecular cloning and characterization. Three transcripts of PHF14 in human cell lines were identified by reverse transcriptase polymerase chain reaction. Two isoforms of PHF14 (PHF14α and PHF14β) were cloned in this study. It was found that PHF14 was ubiquitously expressed in mouse tissues and human cell lines. PHF14α, the major isoform of PHF14, was localized in the nucleus and also bound to chromatin during cell division. Interestingly, co-immunoprecipitation results suggested that PHF14α bound to histones via its PHD fingers. Strikingly, gene-targeting knockout of PHF14 in mice resulted in a neonatal lethality due to respiratory failure. Pathological analysis revealed severe disorders of tissue and cell structures in multiple organs, particularly in the lungs. These results indicated that PHF14 might be an epigenetic regulator and play an important role in the development of multiple organs in mouse.