Stem cell regulatory elements remain bookmarked by selected transcription factors and epigenetic marks during mitosis

Purpose: We investigated the existence, nature and significance of mitotic bookmarking of Klf4, Oct4, Sox2 (KOS) and H3K27ac in mouse ESCs.Methods: DNA-binding/epigenetic profiles of KOS and H3K27ac on asynchronous and mitotic chromatin were generated by deep sequencing following chromatin immunoprecipitation, in replicates.Results: KOS and H3K27ac are largely maintained on mitotic chromatin. KOS bookmark critical stem cell regulatory elements during mitosis. H3K27 acetylation during mitosis is highly retained on promoters of cell cycle and homeostasis related genes and enhancers of genes important for any given cell identity.Conclusions: The extensive mitotic occupancy that we observed is in agreement with a recent study that proposes that TF retention on mitotic chromatin may be a much broader phenomenon than previously appreciated.Bobbie Pelham-Webb is supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH under award number T32GM007739 to the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program. Additionally, this work was funded by the NIH Director s New Innovator Award ( DP2DA043813 ) to Effie Apostolou.