Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA.

Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA.
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通过反义长非编码RNA对Egr 2的转录缓冲调节外周髓鞘形成。

DOI:
10.1016/j.celrep.2017.07.068
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发表时间:
2017-08-22
期刊:
影响因子:
8.8
通讯作者:
Tapinos N
Tapinos N
中科院分区:
生物学1区
文献类型:
--
作者:
Martinez-Moreno M;O'Shea TM;Zepecki JP;Olaru A;Ness JK;Langer R;Tapinos N

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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. Martinez-Moreno et al., report a role for a long non-coding RNA antisense to the promoter of Egr2-AS-RNA, during the response to peripheral nerve injury. Inhibition of the Egr2-AS-RNA following sciatic nerve injury reverts EGR2-mediated gene expression and delays demyelination.
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