論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 28 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-U6-gR-CBh-3xFLAG-PA-dCas9-P2A-puro (RDB14341) |