Format

Send to

Choose Destination
Sci Rep. 2018 Jan 10;8(1):386. doi: 10.1038/s41598-017-18649-4.

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

Author information

1
Department of Molecular Cell Biology, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands.
2
Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands.
3
Leiden Institute of Physics, Leiden University, 2333 RA, Leiden, The Netherlands.
4
Department of Biochemistry, Erasmus University Medical Center, Ee634, 3000CA, Rotterdam, The Netherlands.
5
Department of Molecular Cell Biology, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands. h.mikkers@lumc.nl.

Abstract

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.

PMID:
29321583
PMCID:
PMC5762901
DOI:
10.1038/s41598-017-18649-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center