title: Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development.
abstract: Histone demethylases have emerged as important players in developmental processes. Jumonji domain containing-3 (Jmjd3) has been identified as a key histone demethylase that plays a critical role in the regulation of gene expression; however, the in vivo function of Jmjd3 in embryonic development remains largely unknown. To this end, we generated Jmjd3 global and conditional knockout mice. Global deletion of Jmjd3 induces perinatal lethality associated with defective lung development. Tissue and stage-specific deletion revealed that Jmjd3 is dispensable in the later stage of embryonic lung development. Jmjd3 ablation downregulates the expression of genes critical for lung development and function, including AQP-5 and SP-B. Jmjd3-mediated alterations in gene expression are associated with locus-specific changes in the methylation status of H3K27 and H3K4. Furthermore, Jmjd3 is recruited to the SP-B promoter through interactions with the transcription factor Nkx2.1 and the epigenetic protein Brg1. Taken together, these findings demonstrate that Jmjd3 plays a stage-dependent and locus-specific role in the mouse lung development. Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development.
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors: Qingtian
authors: Q
authors: Li
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors: Helen Y
authors: HY
authors: Wang
authors: Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors: Iouri
authors: I
authors: Chepelev
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors: Qingyuan
authors: Q
authors: Zhu
authors: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Gang
authors: G
authors: Wei
authors: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, United States of America.
authors: Keji
authors: K
authors: Zhao
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors: Rong-Fu
authors: RF
authors: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004265:DNA Helicases / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008239:Lysine; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; D008239:Lysine