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bioRxiv · 10.1101/2022.05.02.490330

EGR2 promoter antisense RNA coordinates chromatin remodeling and spatial genome organization in Schwann cells.

Moreno, M.-M.·Karambizi, D.·Hwang, H.·Fregoso, K.·Chen, J.-S.·Fajardo, J. E.·Fiser, A.·Tapinos, N.
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Abstract

The EGR2 promoter antisense RNA (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 interacts with two distinct histone modification complexes. It binds to EZH2 and WDR5 and enables targeting of H3K27me3 and H3K4me3 to promoters of EGR2and C-JUN respectively. 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 genes. In addition, the EGR2-AS-RNA induces changes in hierarchical TADs and increases transcription factor occupancy on an inter-TAD loop between a super-enhancer regulatory hub and the promoter of mTOR. Our results show that the EGR2-AS-RNA may serve as regulator of chromatin remodeling and spatial genome organization in Schwann cells.

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Moreno, M.-M., Karambizi, D., Hwang, H., Fregoso, K., Chen, J.-S., Fajardo, J. E., Fiser, A., Tapinos, N.. 2022-05-02. EGR2 promoter antisense RNA coordinates chromatin remodeling and spatial genome organization in Schwann cells.. https://doi.org/10.1101/2022.05.02.490330

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