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
リソース情報
実験動物マウス RBRC01252 RBRC03986 RBRC03987 RBRC03988