| First Author | Nakamura T | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 21 | Pages | 4366-78 |
| PubMed ID | 21896782 | Mgi Jnum | J:178324 |
| Mgi Id | MGI:5298147 | Doi | 10.1128/MCB.05701-11 |
| Citation | Nakamura T, et al. (2011) Essential roles of ECAT15-2/Dppa2 in functional lung development. Mol Cell Biol 31(21):4366-78 |
| abstractText | 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. |
