The elusive role of mitotic bookmarking in transcriptional regulation: Insights from Sox2.
The ability of some transcription factors to remain bound to specific genes on condensed mitotic chromosomes has been suggested to play a role in their rapid transcriptional reactivation upon mitotic exit. We have recently shown that SOX2 and OCT4 remain associated to mitotic chromosomes, and that depletion of SOX2 at the mitosis-G1 (M-G1) transition impairs its ability to maintain pluripotency and drive neuroectodermal commitment. Here we report on the role of SOX2 at the M-G1 transition in regulating transcriptional activity of embryonic stem cells. Using single cell time-lapse analysis of reporter constructs for STAT3 and SOX2/OCT4 activity, we show that SOX2/OCT4 do not lead to more rapid transcriptional reactivation in G1 than STAT3, a transcription factor that is excluded from mitotic chromosomes. We also report that only few endogenous target genes show decreased pre-mRNA levels after mitotic exit or in other cell cycle phases in the absence of SOX2 at the M-G1 transition. This suggests that bookmarked SOX2 target genes are not differently regulated than non-bookmarked target genes, and we discuss an alternative hypothesis on how mitotic bookmarking by SOX2 and other sequence-specific transcription factors could be involved in transcriptional regulation.
a UPSUTER , The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology , Lausanne , Switzerland.
Cédric
C
Deluz
a UPSUTER , The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology , Lausanne , Switzerland.
Daniel
D
Strebinger
a UPSUTER , The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology , Lausanne , Switzerland.
Elias T
ET
Friman
a UPSUTER , The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology , Lausanne , Switzerland.
David M
DM
Suter
D000818:Animals; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D007438:Introns / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D012322:RNA Precursors; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; D008156:Luciferases; D015739:Nocodazole
Embryonic stem cells; Sox2; mitotic bookmarking; pluripotency; transcription