TY - JOUR
T1 - Allele-specific repression of Sox2 through the long non-coding RNA Sox2ot
AU - Messemaker, Tobias C
AU - van Leeuwen, Selina M
AU - van den Berg, Patrick R
AU - 't Jong, Anke E J
AU - Palstra, Robert-Jan
AU - Hoeben, Rob C
AU - Semrau, Stefan
AU - Mikkers, Harald M M
PY - 2018/1/10
Y1 - 2018/1/10
N2 - 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.
AB - 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.
KW - Alleles
KW - Animals
KW - Cell Differentiation
KW - Gene Expression Regulation, Developmental
KW - Gene Knock-In Techniques
KW - Mice
KW - Mouse Embryonic Stem Cells/cytology
KW - Neurogenesis
KW - RNA, Long Noncoding/genetics
KW - SOXB1 Transcription Factors/genetics
KW - Transcription, Genetic
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U2 - 10.1038/s41598-017-18649-4
DO - 10.1038/s41598-017-18649-4
M3 - Article
C2 - 29321583
SN - 2045-2322
VL - 8
SP - 386
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 386
ER -