English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency.

MPS-Authors
/persons/resource/persons219545

Poser,  Ina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Atlasi, Y., Megchelenbrink, W., Peng, T., Habibi, E., Joshi, O., Wang, S.-Y., et al. (2019). Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency. Nature cell biology, 21(5), 568-578. doi:10.1038/s41556-019-0310-9.


Cite as: https://hdl.handle.net/21.11116/0000-0006-7D98-3
Abstract
The mechanisms underlying enhancer activation and the extent to which enhancer-promoter 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-promoter 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-Cas9 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.