%0 Journal Article
%T Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency
%J -
%D 2019
%R https://doi.org/10.1038/s41556-019-0310-9
%X The mechanisms underlying enhancer activation and the extent to which enhancer¨Cpromoter rewiring contributes to spatiotemporal gene expression are not well understood. Using integrative and time-resolved analyses we show that the extensive transcriptome and epigenome resetting during the conversion between ¡®serum¡¯ and ¡®2i¡¯ states of mouse embryonic stem cells (ESCs) takes place with minimal enhancer¨Cpromoter rewiring that becomes more evident in primed-state pluripotency. Instead, differential gene expression is strongly linked to enhancer activation via H3K27ac. Conditional depletion of transcription factors and allele-specific enhancer analysis reveal an essential role for Esrrb in H3K27 acetylation and activation of 2i-specific enhancers. Restoration of a polymorphic ESRRB motif using CRISPR¨CCas9 in a hybrid ESC line restores ESRRB binding and enhancer H3K27ac in an allele-specific manner but has no effect on chromatin interactions. Our study shows that enhancer activation in serum- and 2i-ESCs is largely driven by transcription factor binding and epigenetic marking in a hardwired network of chromatin interactions
%U https://www.nature.com/articles/s41556-019-0310-9