美国圣路易斯华盛顿大学Kenneth M. Murphy研究组近期发现，一个Irf8增强子的激活参与控制cDC1细胞命运的分化。相关论文2019年9月发表在《自然—免疫学》上。

经典的1型树突细胞（cDC1）命运分化，需要在共同的树突细胞祖细胞（CDP）中诱导转录因子Irf8，但控制这一诱导的机制尚不清楚。

研究人员通过树突细胞的染色质分析鉴定了Irf8的增强子，并且使用CRISPR/Cas9基因组编辑来评估它们在Irf8调节中的作用。在成熟cDC1中Irf8转录起始位点下游32千碱基（kb）处的增强子活化是该谱系发育所必需的，但不是其分化所需。相反，研究人员发现之前认为仅在浆细胞样树突状细胞中有活性的Irf8下游41kb处的增强子也可在cDC1祖细胞中短暂活跃，并且删除该增强子阻止了CDP中Irf8的诱导并阻止了cDC1分化。因此，树突细胞祖细胞中Irf8下游41kb处增强子的隐蔽激活是cDC1命运分化的原因。

附：英文原文

Title: Cryptic activation of an Irf8 enhancer governs cDC1 fate specification

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

Issue&Volume: Volume 20 Issue 9

Abstract: 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.

DOI: 10.1038/s41590-019-0450-x

Source:https://www.nature.com/articles/s41590-019-0450-x