Cryptic activation of an Irf8 enhancer governs cDC1 fate specification

Durai Vivek; Bagadia Prachi; Granja Jeffrey M.; Satpathy Ansuman T.; Kulkarni Devesha H.; Davidson Jesse T.; Wu Renee; Patel Swapneel J.; Iwata Arifumi; Liu Tian-Tian; Huang Xiao; Briseno Carlos G.; Grajales-Reyes Gary E.; Wohner Miriam; Tagoh Hiromi; Kee Barbara L.; Newberry Rodney D.; Busslinger Meinrad; Chang Howard Y.; Murphy Theresa L.; Murphy Kenneth M.

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Cryptic activation of an Irf8 enhancer governs cDC1 fate specification

机译：IRF8增强器的密码激活管理CDC1命运规范

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Induction of the transcription factor Irf8 in the common dendritic cell progenitor (CDP) is required for classical type 1 dendritic cell (cDC1) fate specification, but the mechanisms controlling this induction are unclear. In the present study Irf8 enhancers were identified via chromatin profiling of dendritic cells and CRISPR/Cas9 genome editing was used to assess their roles in Irf8 regulation. An enhancer 32 kilobases (kb) downstream of the Irf8 transcriptional start site (+32-kb Irf8) that was active in mature cDC1s was required for the development of this lineage, but not for its specification. Instead, a +41-kb Irf8 enhancer, previously thought to be active only in plasmacytoid dendritic cells, was found to also be transiently accessible in cDC1 progenitors, and deleting this enhancer prevented the induction of Irf8 in CDPs and abolished cDC1 specification. Thus, cryptic activation of the +41-kb Irf8 enhancer in dendritic cell progenitors is responsible for cDC1 fate specification.

机译：常规树枝状细胞祖细胞（CDP）中的转录因子IRF8的诱导是古典1树突细胞（CDC1）命运规范所必需的，但控制该诱导的机制尚不清楚。在本研究中，IRF8通过树突细胞的染色质分析鉴定IRF8增强剂，并使用CRISPR / CAS9基因组编辑来评估其在IRF8调节中的作用。在成熟的CDC1S中有效的IRF8转录起始位点（+ 32-KB IRF8）下游的增强子32千碱基（KB）是为了开发这种谱系，但不能用于其规格。相反，+ 41-kB IRF8增强剂以前认为仅在血浆曲线细胞中有活性，发现在CDC1祖细胞中也可瞬时可释放，并且缺失该增强剂阻止了CDPS中的IRF8并废除了CDC1规格。因此，树突细胞祖细胞中+ 41-kB IRF8增强剂的密码激活是CDC1命运规范的原因。

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《Nature immunology》 |2019年第9期|共20页
作者
Durai Vivek; Bagadia Prachi; Granja Jeffrey M.; Satpathy Ansuman T.; Kulkarni Devesha H.; Davidson Jesse T.; Wu Renee; Patel Swapneel J.; Iwata Arifumi; Liu Tian-Tian; Huang Xiao; Briseno Carlos G.; Grajales-Reyes Gary E.; Wohner Miriam; Tagoh Hiromi; Kee Barbara L.; Newberry Rodney D.; Busslinger Meinrad; Chang Howard Y.; Murphy Theresa L.; Murphy Kenneth M.;
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作者单位

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Stanford Univ Sch Med Ctr Personal Dynam Regulomes Stanford CA 94305 USA;

Stanford Univ Sch Med Ctr Personal Dynam Regulomes Stanford CA 94305 USA;

Washington Univ Sch Med John T Milliken Dept Med Div Gastroenterol St Louis MO USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med John T Milliken Dept Med Div Rheumatol St Louis MO USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Res Inst Mol Pathol Campus Vienna Bioctr 1 Vienna Austria;

Res Inst Mol Pathol Campus Vienna Bioctr 1 Vienna Austria;

Univ Chicago Dept Pathol 5841 S Maryland Ave Chicago IL 60637 USA;

Washington Univ Sch Med John T Milliken Dept Med Div Gastroenterol St Louis MO USA;

Res Inst Mol Pathol Campus Vienna Bioctr 1 Vienna Austria;

Stanford Univ Sch Med Ctr Personal Dynam Regulomes Stanford CA 94305 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

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正文语种 eng
中图分类医学免疫学;
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1. Cryptic activation of an Irf8 enhancer governs cDC1 fate specification [J] . Durai Vivek, Bagadia Prachi, Granja Jeffrey M., Nature immunology . 2019,第9期

机译：IRF8增强器的密码激活管理CDC1命运规范
2. An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development [J] . Bagadia Prachi, Huang Xiao, Liu Tian-Tian, Nature immunology . 2019,第9期

机译：NFIL3-ZEB2-ID2路径在CDC1开发期间施加IRF8增强器切换
3. Priority lane to cDC1 open for IRF8(+) progenitors [J] . Guilliams Martin, Scott Charlotte L. Blood: The Journal of the American Society of Hematology . 2019,第17期

机译：优先道到CDC1为IRF8（+）祖细胞开放
4. THE BRAER SPILL: OIL FATE GOVERNED BY DISPERSION [C] . T. Lunel . 2005

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5. Fate's grim intervention: Determining sibling relationships and mechanisms of cell fate specification in the NB7-3 lineage of the Drosophila embryonic CNS. [D] . Karcavich, Rachel Elaine. 2001

机译：命运的严峻干预：确定果蝇胚胎CNS的NB7-3谱系中的兄弟关系和细胞命运规范的机制。
6. Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro [O] . Diana M. Elizondo, Nailah Z. D. Brandy, Ricardo L. L. da Silva, -1

机译：同种异体炎症因子-1通过体外IRF8和RelB控制造血干细胞分化为cDC1和单核细胞衍生的树突状细胞。
7. Cryptic activation of an Irf8 enhancer governs cDC1 fate specification [O] . Vivek Durai, Prachi Bagadia, Jeffrey M. Granja, 2019

机译：IRF8增强器的密码激活管理CDC1命运规范

Cryptic activation of an Irf8 enhancer governs cDC1 fate specification

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