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

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. Overall design: We performed RNA-seq on Schwann cells after ectopic expression of the Egr2-AS-RNA to determine changes in gene expression. Upregulated genes were enriched for mTOR signaling and cell cycling biological processes. Downregulated genes were enriched for Erk1/Erk2 signaling, ErbB signaling pathway, MAPK regulation and ECM organization biological processes. Additionally, upregulated genes showed enrichment for sonic hedgehog (Shh) signaling pathway.