Essential roles of ECAT15-2/Dppa2 in functional lung development.
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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.
Journal
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- Molecular and cellular biology
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Molecular and cellular biology 31 (21), 4366-4378, 2011-11
American Society for Microbiology
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Keywords
- Animals
- Binding Sites/genetics
- Embryonic Stem Cells/metabolism
- Epigenesis, Genetic
- Female
- Gene Expression Regulation, Developmental
- 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
Details 詳細情報について
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- CRID
- 1050564285679676544
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- NII Article ID
- 120003674151
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- NII Book ID
- AA10620925
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- ISSN
- 02707306
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- HANDLE
- 2433/152301
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles