小柯机器人

美国华盛顿大学圣路易斯医学院Kenneth M. Murphy及其研究小组发现，大量转录因子IRF8参与AP1-IRF复合元件组成的增强子，以直接调控1型经典树突状细胞的身份。相关论文于2020年8月13日在线发表在《免疫》杂志上。

在本研究中，研究人员揭示了IRF8和IRF4在cDC发育过程中产生不同作用的基础。由cDC1和cDC2共表达的基因使用EICE依赖的增强子，这些增强子被少量IRF4或IRF8冗余激活。相比之下，cDC1特异性基因利用AICE依赖性增强子，这需要高浓度IRF，但其可被IRF4或IRF8激活。仅少数cDC1特异性基因（例如Xcr1）才需要IRF8，这些基因可以区分IRF8和IRF4 的DNA结合结构域。

因此，这些结果解释了依赖BATF3的Irf8自激活如何引起cDC1特异性基因转录的开启。

据了解，cDC亚型cDC1和cDC2的发育和功能分别取决于转录因子（TF）IRF8和IRF4。由于IRF8和IRF4各自可以与AP1-IRF复合元件（AICE）中的TF BATF3相互作用，以及与Ets-IRF复合元件（EICEs）中的TF PU.1相互作用，因此尚不清楚这些因子如何发挥不同的功能。

附：英文原文

Title: High Amount of Transcription Factor IRF8 Engages AP1-IRF Composite Elements in Enhancers to Direct Type 1 Conventional Dendritic Cell Identity

Author: Sunkyung Kim, Prachi Bagadia, David A. Anderson, Tian-Tian Liu, Xiao Huang, Derek J. Theisen, Kevin W. O’Connor, Ray A. Ohara, Arifumi Iwata, Theresa L. Murphy, Kenneth M. Murphy

Issue&Volume: 2020-08-13

Abstract: Development and function of conventional dendritic cell (cDC) subsets, cDC1 and cDC2,depend on transcription factors (TFs) IRF8 and IRF4, respectively. Since IRF8 andIRF4 can each interact with TF BATF3 at AP1-IRF composite elements (AICEs) and withTF PU.1 at Ets-IRF composite elements (EICEs), it is unclear how these factors exertdivergent actions. Here, we determined the basis for distinct effects of IRF8 andIRF4 in cDC development. Genes expressed commonly by cDC1 and cDC2 used EICE-dependentenhancers that were redundantly activated by low amounts of either IRF4 or IRF8. Bycontrast, cDC1-specific genes relied on AICE-dependent enhancers, which required highIRF concentrations, but were activated by either IRF4 or IRF8. IRF8 was specificallyrequired only by a minority of cDC1-specific genes, such as Xcr1, which could distinguish between IRF8 and IRF4 DNA-binding domains. Thus, these resultsexplain how BATF3-dependent Irf8 autoactivation underlies emergence of the cDC1-specific transcriptional program.

DOI: 10.1016/j.immuni.2020.07.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30325-3

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