| RRC ID |
87229
|
| 著者 |
Murakami K, Sasaki H, Nishiyama A, Kurotaki D, Kawase W, Ban T, Nakabayashi J, Kanzaki S, Sekita Y, Nakajima H, Ozato K, Kimura T, Tamura T.
|
| タイトル |
A RUNX-CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes.
|
| ジャーナル |
Nat Immunol
|
| Abstract |
The transcription factor IRF8 is essential for the development of monocytes and dendritic cells (DCs), whereas it inhibits neutrophilic differentiation. It is unclear how Irf8 expression is regulated and how this single transcription factor supports the generation of both monocytes and DCs. Here, we identified a RUNX-CBFβ-driven enhancer 56 kb downstream of the Irf8 transcription start site. Deletion of this enhancer in vivo significantly decreased Irf8 expression throughout the myeloid lineage from the progenitor stages, thus resulting in loss of common DC progenitors and overproduction of Ly6C+ monocytes. We demonstrated that high, low or null expression of IRF8 in hematopoietic progenitor cells promotes differentiation toward type 1 conventional DCs, Ly6C+ monocytes or neutrophils, respectively, via epigenetic regulation of distinct sets of enhancers in cooperation with other transcription factors. Our results illustrate the mechanism through which IRF8 controls the lineage choice in a dose-dependent manner within the myeloid cell system.
|
| 巻・号 |
22(3)
|
| ページ |
301-311
|
| 公開日 |
2021-3-1
|
| DOI |
10.1038/s41590-021-00871-y
|
| PII |
10.1038/s41590-021-00871-y
|
| PMID |
33603226
|
| MeSH |
Animals
Antigens, Ly / genetics
Antigens, Ly / metabolism
Bone Marrow Cells
Cell Lineage*
Cells, Cultured
Core Binding Factor alpha Subunits / genetics
Core Binding Factor alpha Subunits / metabolism*
Core Binding Factor beta Subunit / genetics
Core Binding Factor beta Subunit / metabolism*
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Enhancer Elements, Genetic*
Epigenesis, Genetic
Female
Gene Expression Regulation, Developmental
Interferon Regulatory Factor-8
Interferon Regulatory Factors / deficiency
Interferon Regulatory Factors / genetics
Interferon Regulatory Factors / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Monocytes / immunology
Monocytes / metabolism*
Myeloid Progenitor Cells / immunology
Myeloid Progenitor Cells / metabolism*
Phenotype
Signal Transduction
|
| IF |
20.479
|
| リソース情報 |
| 遺伝子材料 |
CSII-U6-gR-CBh-3xFLAG-PA-dCas9-P2A-puro (RDB14341) |
