Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

PLoS One. 2017 Jul 12;12(7):e0180579. doi: 10.1371/journal.pone.0180579. eCollection 2017.

Abstract

The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE), and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Anilides / pharmacology
  • Animals
  • Brain / embryology
  • Brain / metabolism
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Nitriles / pharmacology
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Receptors, Androgen / metabolism*
  • Response Elements
  • Tosyl Compounds / pharmacology
  • Transcriptional Activation*

Substances

  • Androgen Antagonists
  • Anilides
  • Nitriles
  • RNA, Long Noncoding
  • Receptors, Androgen
  • Tosyl Compounds
  • long noncoding RNA Sox2OT, mouse
  • bicalutamide

Grants and funding

This work was funded by Regione Lombardia (to D.P., EA.P.); Fondazione IRCCS Istituto Neurologico Carlo Besta (to EA.P), University of Milan (to A.G.) and IRCCS San Raffaele Hospital (to C. DR.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.