論文 - 詳細
| RRC ID | 11796 |
|---|---|
| 著者 | Fujii T, Ueda T, Nagata S, Fukunaga R. |
| タイトル | Essential role of p400/mDomino chromatin-remodeling ATPase in bone marrow hematopoiesis and cell-cycle progression. |
| ジャーナル | J Biol Chem |
| Abstract |
p400/mDomino is an ATP-dependent chromatin-remodeling protein that catalyzes the deposition of histone variant H2A.Z into nucleosomes to regulate gene expression. We previously showed that p400/mDomino is essential for embryonic development and primitive hematopoiesis. Here we generated a conditional knock-out mouse for the p400/mDomino gene and investigated the role of p400/mDomino in adult bone marrow hematopoiesis and in the cell-cycle progression of embryonic fibroblasts. The Mx1-Cre- mediated deletion of p400/mDomino resulted in an acute loss of nucleated cells in the bone marrow, including committed myeloid and erythroid cells as well as hematopoietic progenitor and stem cells. A hematopoietic colony assay revealed a drastic reduction in colony-forming activity after the deletion of p400/mDomino. Moreover, the loss of p400/mDomino in mouse embryonic fibroblasts (MEFs) resulted in strong growth inhibition. Cell-cycle analysis revealed that the mDomino-deficient MEFs exhibited a pleiotropic cell-cycle defect at the S and G(2)/M phases, and polyploid and multi-nucleated cells with micronuclei emerged. DNA microarray analysis revealed that the p400/mDomino deletion from MEFs caused the impaired expression of many cell-cycle-regulatory genes, including G(2)/M-specific genes targeted by the transcription factors FoxM1 and c-Myc. These results indicate that p400/mDomino plays a key role in cellular proliferation by controlling the expression of cell-cycle-regulatory genes. |
| 巻・号 | 285(39) |
| ページ | 30214-23 |
| 公開日 | 2010-9-24 |
| DOI | 10.1074/jbc.M110.104513 |
| PII | S0021-9258(19)89057-9 |
| PMID | 20610385 |
| PMC | PMC2943321 |
| MeSH | Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism* Animals Cell Cycle / physiology* Chromatin Assembly and Disassembly / physiology* DNA Helicases DNA-Binding Proteins Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Erythroid Cells / cytology Erythroid Cells / metabolism Fibroblasts / cytology Fibroblasts / metabolism Forkhead Box Protein M1 Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Hematopoiesis / physiology* Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / metabolism* Histones / genetics Histones / metabolism Mice Mice, Knockout Myeloid Cells / cytology Myeloid Cells / metabolism Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 4.238 |
| 引用数 | 18 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01252 RBRC03986 RBRC03987 RBRC03988 |