biostudies-literatureHe HNational Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint FundNHLBI NIH HHSNational Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)8112https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405758biostudies-literatureUnknown15(1)While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT2Nature communicationsPRDM3/16 regulate chromatin accessibility required for NKX2-1 mediated alveolar epithelial differentiation and function.PMC1140575882200098R01HL164414R01 HL164414Na CLGuo MDavis AKZhao SSwarr DTZacharias WJHe HSridharan ABell SMXu YSnowball JWhitsett JAfalsePRDM3/16 regulate chromatin accessibility required for NKX2-1 mediated alveolar epithelial differentiation and function.While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT22024-01-01T00:00:00Z2024 Sep2026-06-02T22:21:18.81Z2025-04-06T12:29:41.567ZS-EPMC114057583928479810.1038/s41467-024-52154-3