Zhang, HuiGayen, SrimontaXiong, JieZhou, BoShanmugam, Avinash K.Sun, YuqingKaratas, HacerLiu, LiuRao, Rajesh C.Wang, ShaomengNesvizhskii, Alexey I.Kalantry, SundeepDou, Yali2016-07-192016-07-192016-07-19201610.1016/j.stem.2016.02.004https://infoscience.epfl.ch/handle/20.500.14299/127272WOS:000373722100012The interconversion between naive and primedpluripotent states is accompanied by drastic epigeneticrearrangements. Howeverit is unclear whetherintrinsic epigenetic events can drive reprogrammingto naive pluripotency or if distinct chromatin statesare instead simply a reflection of discrete pluripotentstates. Herewe show that blocking histone H3K4methyltransferase MLL1 activity with the smallmoleculeinhibitor MM-401 reprograms mouse epiblaststem cells (EpiSCs) to naive pluripotency. This reversionis highly efficient and synchronizedwith morethan 50% of treated EpiSCs exhibiting features ofnaive embryonic stem cells (ESCs) within 3 days. RevertedESCs reactivate the silenced X chromosomeand contribute to embryos following blastocyst injectiongenerating germlinecompetent chimeras.Importantlyblocking MLL1 leads to global redistributionof H3K4me1 at enhancers and represses lineagedeterminant factors and EpiSC markerswhichindirectly regulate ESC transcription circuitry. Thesefindings show that discrete perturbation of H3K4methylation is sufficient to drive reprogramming tonaive pluripotency.text::journal::journal article::research article