Summary
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 the Egr2-AS-RNA in DRG cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of the 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. The Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2 and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of the Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to the Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in PNS biology.
Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion by demyelinating and converting into repair cells that secrete neurotrophic factors and guide axons back to their former target to finally remyelinate regenerated axons. The different steps of SC development and their role in the maintenance of PNS integrity and regeneration after lesion are controlled by various factors among which transcription factors and chromatin‐remodeling enzymes hold major functions. In this review, we discussed how histone modifications and histone‐modifying enzymes control SC development, maintenance of PNS integrity and response to injury. The functions of histone modifiers as part of chromatin‐remodeling complexes are discussed in another review published in the same issue of Glia.
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