title: Essential roles of ECAT15-2/Dppa2 in functional lung development.
abstract: Many transcription factors and DNA binding proteins play essential roles in the development of organs in which they are highly and/or specifically expressed. Embryonic stem cell (ESC)-associated transcript 15-1 (ECAT15-1) and ECAT15-2, also known as developmental pluripotency-associated 4 (Dppa4) and Dppa2, respectively, are enriched in mouse ESCs and preimplantation embryos, and their genes encode homologous proteins with a common DNA binding domain known as the SAP motif. Previously, ECAT15-1 was shown to be important in lung development, while it is dispensable in early development. In this study, we generated ECAT15-2 single and ECAT15-1 ECAT15-2 double knockout (double KO) mice and found that almost all mutants, like ECAT15-1 mutants, died around birth with respiratory defects. Paradoxically, the expression of neither ECAT15-1 nor ECAT15-2 was detected in lung organogenesis. Several genes, such as Nkx2-5, Gata4, and Pitx2, were downregulated in the ECAT15-2-null lung. On the other hand, genomic DNA of these genes showed inactive chromatin statuses in ECAT15-2-null ESCs, but not in wild-type ESCs. The chromatin immunoprecipitation (ChIP) assay revealed that ECAT15-2 binds to the regulatory region of Nkx2-5 in ESCs. These data suggest that ECAT15-2 has important roles in lung development, where it is no longer expressed, by leaving epigenetic marks from earlier developmental stages.
authors: Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
authors: Tomonori
authors: T
authors: Nakamura
authors: Masato
authors: M
authors: Nakagawa
authors: Tomoko
authors: T
authors: Ichisaka
authors: Arufumi
authors: A
authors: Shiota
authors: Shinya
authors: S
authors: Yamanaka
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D008168:Lung / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics
chemical_list: C519286:Dppa2 protein, mouse; C519287:Dppa4 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors