L-Myc expression by dendritic cells is required for optimal T-cell priming. Mus musculus

The transcription factor IRF8 is a critical regulator of plasmacytoid dendritic cell (pDC) and classical dendritic cell (cDC) development in both mouse and man. Yet the downstream molecular targets that regulate DC homeostasis and development are largely unknown. A recent study using gene expression analysis of IRF8-deficient myeloid and lymphoid progenitors identified the Myc paralog Mycl1 as a potential transcriptional target of IRF8. We report here that Mycl1 is a mediator of DC homeostasis at steady state and during inflammation, and its expression is regulated by IRF8 in multiple DC lineages. We have further validated these observations with ChIP-Seq of IRF8 binding to the Mycl1 locus. Notably, IRF8 binding to Mycl1 locus is independent of an interaction with the AP1 factor, BATF3. Additionally, our genome-wide survey of IRF8 binding identified both EICE and AICE motifs. Overall design: Examination of IRF8 binding in dendritic cells

转录因子IRF8是小鼠与人类体内浆细胞样树突状细胞（plasmacytoid dendritic cell, pDC）及经典树突状细胞（classical dendritic cell, cDC）发育的关键调控因子。然而，调控树突状细胞（DC）稳态与发育的下游分子靶点仍在很大程度上尚未明确。近期一项针对IRF8缺陷型髓系及淋巴系祖细胞的基因表达分析研究，将MYC旁系同源基因Mycl1鉴定为IRF8的潜在转录靶点。本研究发现，Mycl1是稳态状态下及炎症过程中树突状细胞稳态的调控介质，且在多种树突状细胞谱系中，其表达均受IRF8调控。我们通过IRF8结合Mycl1基因座的染色质免疫沉淀测序（ChIP-Seq）实验，进一步验证了上述观测结果。值得注意的是，IRF8与Mycl1基因座的结合无需与AP1因子BATF3发生相互作用。此外，我们在全基因组范围内对IRF8结合位点进行的筛查，同时鉴定出了EICE基序与AICE基序。实验设计：检测树突状细胞中的IRF8结合情况