Egr2 promoter antisense RNA as coordinator of chromatin remodeling and genome reorganization in Schwann cells [Hi-C]

The Egr2 promoter antisense RNA (Egr2-AS-RNA) recruits chromatin remodeling complexes to inhibit Egr2 transcription following peripheral nerve injury. Here we show that the Egr2-AS-RNA modulates chromatin accessibility and serves as scaffold for two distinct histone modification complexes. The Egr2-AS-RNA binds to Ezh2 and Wdr5 and enables coordinate targeting of H3K27me3 and H3K4me3 to promoters of Egr2 and c-Jun. Expression of the AS-RNA results in reorganization of the global chromatin landscape and quantitative changes in loop formation and in contact frequency at domain boundaries exhibiting enrichment for AP-1 binding events. Our results show for the first time that the Egr2 promoter AS-RNA may serve as a regulator of coordinate chromatin remodeling and genome organization to regulate transcription, with a significant role in phenotypic plasticity of SCs.Egr2启动子反义RNA（Egr2 promoter antisense RNA，缩写Egr2-AS-RNA）可招募染色质重塑复合物，在周围神经损伤后抑制Egr2的转录。本研究发现，Egr2-AS-RNA可调控染色质可及性，并作为支架分子结合两种不同的组蛋白修饰复合物。Egr2-AS-RNA可结合增强子zeste同源物2（Ezh2）与WD重复结构域蛋白5（Wdr5），并实现组蛋白H3第27位赖氨酸三甲基化（H3K27me3）与组蛋白H3第4位赖氨酸三甲基化（H3K4me3）协同靶向Egr2与c-Jun的启动子区域。该反义RNA的表达可引发全局染色质景观的重塑，并在富集激活蛋白1（Activator Protein 1，AP-1）结合事件的染色质结构域边界处，导致环结构形成与接触频率出现定量改变。本研究首次证实，Egr2启动子反义RNA可作为协同调控染色质重塑与基因组组织的转录调控因子，在施万细胞（Schwann cells，SCs）的表型可塑性中发挥重要作用。