1. Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA
- Author
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Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, O'Shea, Timothy Mark, Langer, Robert S, Martinez-Moreno, Margot, Zepecki, John P., Olaru, Alexander, Ness, Jennifer K., Tapinos, Nikos, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, O'Shea, Timothy Mark, Langer, Robert S, Martinez-Moreno, Margot, Zepecki, John P., Olaru, Alexander, Ness, Jennifer K., and Tapinos, Nikos
- Abstract
Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS) biology. Keywords: nerve injury response; transcription; RNA epigenetics; antisense RNA; Egr2; myelination; YY1; neuregulin
- Published
- 2018