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

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  • معلومة اضافية
    • Contributors:
      Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Koch Institute for Integrative Cancer Research at MIT; O'Shea, Timothy Mark; Langer, Robert S
    • بيانات النشر:
      Elsevier
    • الموضوع:
      2018
    • Collection:
      DSpace@MIT (Massachusetts Institute of Technology)
    • نبذة مختصرة :
      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
    • File Description:
      application/pdf
    • ISSN:
      2211-1247
    • Relation:
      http://dx.doi.org/10.1016/J.CELREP.2017.07.068; Cell Reports; http://hdl.handle.net/1721.1/114935; Martinez-Moreno, Margot et al. “Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-Coding RNA.” Cell Reports 20, 8 (August 2017): 1950–1963 © 2017 The Authors; orcid:0000-0003-4255-0492
    • الدخول الالكتروني :
      http://hdl.handle.net/1721.1/114935
    • Rights:
      Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) ; https://creativecommons.org/licenses/by-nc-nd/4.0/
    • الرقم المعرف:
      edsbas.947EBFAB