| RRC ID |
56681
|
| 著者 |
Yashiro T, Kasakura K, Oda Y, Kitamura N, Inoue A, Nakamura S, Yokoyama H, Fukuyama K, Hara M, Ogawa H, Okumura K, Nishiyama M, Nishiyama C.
|
| タイトル |
The hematopoietic cell-specific transcription factor PU.1 is critical for expression of CD11c.
|
| ジャーナル |
Int Immunol
|
| Abstract |
PU.1 is a hematopoietic cell-specific transcription factor belonging to the Ets family, which plays an important role in the development of dendritic cells (DCs). CD11c (encoded by Itgax) is well established as a characteristic marker of hematopoietic lineages including DCs. In the present study, we analyzed the role of PU.1 (encoded by Spi-1) in the expression of CD11c. When small interfering RNA (siRNA) for Spi-1 was introduced into bone marrow-derived DCs (BMDCs), the mRNA level and cell surface expression of CD11c were dramatically reduced. Using reporter assays, the TTCC sequence at -56/-53 was identified to be critical for PU.1-mediated activation of the promoter. An EMSA showed that PU.1 directly bound to this region. ChIP assays demonstrated that a significant amount of PU.1 bound to this region on chromosomal DNA in BMDCs, which was decreased in LPS-stimulated BMDCs in accordance with the reduced levels of mRNAs of Itgax and Spi-1, and the histone acetylation degree. Enforced expression of exogenous PU.1 induced the expression of the CD11c protein on the cell surface of mast cells, whereas control transfectants rarely expressed CD11c. Quantitative RT-PCR also showed that the expression of a transcription factor Irf4, which is a partner molecule of PU.1, was reduced in PU.1-knocked down BMDCs. IRF4 transactivated the Itgax gene in a synergistic manner with PU.1. Taken together, these results indicate that PU.1 functions as a positive regulator of CD11c gene expression by directly binding to the Itgax promoter and through transactivation of the Irf4 gene.
|
| 巻・号 |
29(2)
|
| ページ |
87-94
|
| 公開日 |
2017-2-1
|
| DOI |
10.1093/intimm/dxx009
|
| PII |
3045847
|
| PMID |
28338898
|
| MeSH |
Acetylation
Animals
CD11c Antigen / genetics
CD11c Antigen / metabolism*
Cells, Cultured
DNA-Binding Proteins / genetics
Dendritic Cells / physiology*
Gene Expression Regulation
Hematopoiesis* / genetics
Histones / metabolism
Interferon Regulatory Factors / genetics
Interferon Regulatory Factors / metabolism*
Mice
Mice, Inbred BALB C
Organ Specificity
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
RNA, Small Interfering / genetics
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcriptional Activation
|
| IF |
4.168
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
CV-1(RCB0160) |
