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

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.

Allele-specific repression of Sox2 through the long non-coding RNA Sox2ot

“…Primers recognizing an exon of Sox2otb that also is the first exon of Sox2otc could amplify Sox2ot transcripts in early passage neurospheres (data not shown and Fig. 1g ), which is in agreement with two recent studies 31 , 35 . Using 5′ RLM-RACE we confirmed the 5′ ends of Sox2otb and Sox2otc (Supplementary Fig.…”

Invited Review: Long non‐coding RNAs: important regulators in the development, function and disorders of the central nervous system

“…Additionally, Fantes et al found that the Sox2 gene is contained within an intron of Sox2ot (Sox2 overlapping transcript) lncRNA and both genes are transcribed in the same direction [97]. Recent reports have demonstrated the transcriptional regulation of Sox2 expression by Sox2ot in various biological contexts including neural differentiation [98][99][100][101][102][103]. These mechanisms demonstrate the diverse ways in which lncRNAs can control complex differentiation programs.…”

The functions of long non-coding RNAs in neural stem cell proliferation and differentiation

“…Sox1ot and Sox2ot are highly expressed during neural development and link with Sox1 and Sox2 expression levels, respectively [53,54]. Androgen receptor (AR),a transcription regulator in early embryonic stage, modulates lncRNA Sox2ot expression by interacting with Sox2 upstream DNA binding region at transcription level [55]. LncRNA Sox2ot prohibited NSCs proliferation and advanced neuronal differentiation by interacting with the transcriptional regulator YY1, which bind to CpG island in the Sox2 locus to suppress the expression of Sox2 [54].…”