RRC ID |
11796
|
Author |
Fujii T, Ueda T, Nagata S, Fukunaga R.
|
Title |
Essential role of p400/mDomino chromatin-remodeling ATPase in bone marrow hematopoiesis and cell-cycle progression.
|
Journal |
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.
|
Volume |
285(39)
|
Pages |
30214-23
|
Published |
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
|
Times Cited |
18
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Mice |
RBRC01252
RBRC03986
RBRC03987
RBRC03988 |