Essential roles of ECAT15-2/Dppa2 in functional lung development

Mol Cell Biol. 2011 Nov;31(21):4366-78. doi: 10.1128/MCB.05701-11. Epub 2011 Sep 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Embryonic Stem Cells / metabolism
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / genetics
  • Lung / abnormalities
  • Lung / embryology*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Pregnancy
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / genetics


  • Dppa2 protein, mouse
  • Dppa4 protein, mouse
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Nuclear Proteins
  • Transcription Factors

Associated data

  • GEO/GSE31584