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

Yaser Atlasi, Wout Megchelenbrink, Tianran Peng, Ehsan Habibi, Onkar Joshi, Shuang-Yin Wang, Cheng Wang, Colin Logie, Ina Poser, Hendrik Marks, Hendrik G Stunnenberg

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)568-578
Number of pages11
JournalNature Cell Biology
Volume21
Issue number5
DOIs
Publication statusPublished - 29 Apr 2019
Externally publishedYes

Keywords

  • Animals
  • CRISPR-Cas Systems/genetics
  • Cell Differentiation/genetics
  • Chromatin/genetics
  • Enhancer Elements, Genetic
  • Epigenesis, Genetic
  • Histones/genetics
  • Mice
  • Mouse Embryonic Stem Cells/metabolism
  • Pluripotent Stem Cells
  • Promoter Regions, Genetic
  • Receptors, Estrogen/genetics
  • Transcriptome/genetics

Fingerprint Dive into the research topics of 'Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency'. Together they form a unique fingerprint.

  • Cite this

    Atlasi, Y., Megchelenbrink, W., Peng, T., Habibi, E., Joshi, O., Wang, S-Y., Wang, C., Logie, C., Poser, I., Marks, H., & Stunnenberg, H. G. (2019). Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency. Nature Cell Biology, 21(5), 568-578. https://doi.org/10.1038/s41556-019-0310-9