The transcription factor Sox2 controls the fate of pluripotent stem cells and neural stem cells. This gatekeeper function requires well-regulated Sox2 levels. We postulated that Sox2 regulation is partially controlled by the Sox2 overlapping long non-coding RNA (lncRNA) gene Sox2ot. Here we show that the RNA levels of Sox2ot and Sox2 are inversely correlated during neural differentiation of mouse embryonic stem cells (ESCs). Through allele-specific enhanced transcription of Sox2ot in mouse Sox2eGFP knockin ESCs we demonstrate that increased Sox2ot transcriptional activity reduces Sox2 RNA levels in an allele-specific manner. Enhanced Sox2ot transcription, yielding lower Sox2 RNA levels, correlates with a decreased chromatin interaction of the upstream regulatory sequence of Sox2 and the ESC-specific Sox2 super enhancer. Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development.

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Journal Scientific Reports
Messemaker, T.C. (Tobias), Leeuwen, S.M. (Selina) van, Berg, P.R. (Patrick) van den, Jong, A.E.J.T. (Anke E.J.T.), Palstra, R.-J.T.S, Hoeben, R.C, … Mikkers, H. (2018). Allele-specific repression of Sox2 through the long non-coding RNA Sox2ot. Scientific Reports, 8(1). doi:10.1038/s41598-017-18649-4