Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.
Equipe Labellisée Ligue Contre le Cancer, Paris, France.
Nat Commun. 2021 Nov 18;12(1):6660. doi: 10.1038/s41467-021-26861-0.
Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.
基因表达受基因近端（启动子）和远端（增强子）调控元件的参与调控。我们之前的研究结果表明，一组称为 Epromoters 的基因启动子作为真正的增强子起作用，并调节远端基因表达。在这里，我们假设 Epromoters 在炎症反应中快速诱导基因的协调中起着关键作用。我们使用高通量报告基因检测方法研究了 Epromoters 在 I 型干扰素反应中的功能。我们发现，IFNa 诱导的基因簇经常与 Epromoters 相关，并且这些调节元件优先招募 STAT1/2 和 IRF 转录因子，并在远端调节干扰素反应基因的激活。一致地，我们鉴定并验证了 Epromoter 包含的簇在 LPS 刺激的巨噬细胞中的调控作用。我们的研究结果表明，Epromoters 作为一个局部枢纽，募集炎症反应过程中协调调控基因簇所需的关键 TF。
