| RRC ID |
21801
|
| Author |
Nakashima K, Arai S, Suzuki A, Nariai Y, Urano T, Nakayama M, Ohara O, Yamamura K, Yamamoto K, Miyazaki T.
|
| Title |
PAD4 regulates proliferation of multipotent haematopoietic cells by controlling c-myc expression.
|
| Journal |
Nat Commun
|
| Abstract |
Peptidylarginine deiminase 4 (PAD4) functions as a transcriptional coregulator by catalyzing the conversion of histone H3 arginine residues to citrulline residues. Although the high level of PAD4 expression in bone marrow cells suggests its involvement in haematopoiesis, its precise contribution remains unclear. Here we show that PAD4, which is highly expressed in lineage(-) Sca-1(+) c-Kit(+) (LSK) cells of mouse bone marrow compared with other progenitor cells, controls c-myc expression by catalyzing the citrullination of histone H3 on its promoter. Furthermore, PAD4 is associated with lymphoid enhancer-binding factor 1 and histone deacetylase 1 at the upstream region of the c-myc gene. Supporting these findings, LSK cells, especially multipotent progenitors, in PAD4-deficient mice show increased proliferation in a cell-autonomous fashion compared with those in wild-type mice. Together, our results strongly suggest that PAD4 regulates the proliferation of multipotent progenitors in the bone marrow by controlling c-myc expression.
|
| Volume |
4
|
| Pages |
1836
|
| Published |
2013-1-1
|
| DOI |
10.1038/ncomms2862
|
| PII |
ncomms2862
|
| PMID |
23673621
|
| PMC |
PMC3674250
|
| MeSH |
Animals
Cell Count
Cell Nucleus / enzymology
Cell Proliferation
HEK293 Cells
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / enzymology*
Histone Deacetylases / metabolism
Humans
Hydrolases / deficiency
Hydrolases / metabolism*
Lymphoid Enhancer-Binding Factor 1 / metabolism
Mice
Mice, Inbred C57BL
Multipotent Stem Cells / cytology*
Multipotent Stem Cells / enzymology*
Promoter Regions, Genetic / genetics
Protein Transport
Protein-Arginine Deiminase Type 4
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism*
|
| IF |
12.121
|
| Times Cited |
26
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Mice |
RBRC00144 |
