Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent...

Area of Science:

• Genomics
• Molecular Biology
• Developmental Biology

Background:

• Transcriptional enhancers, particularly super-enhancers (SEs), are crucial for cell-type-specific gene expression by interacting with gene promoters.
• SEs are defined by high transcription factor binding and active chromatin, with target promoters often predicted computationally.
• The dynamics of promoter-SE interactions during cell state changes and the role of transcription factors in maintaining these interactions remain largely unexplored.

Purpose of the Study:

• To investigate how promoter-super-enhancer (SE) interactions are structured and how they change during cell state transitions in mouse embryonic stem cells (ESCs).
• To determine the role of core transcription factors in maintaining these promoter-SE interactions.

Main Methods:

• Utilized promoter-capture Hi-C technology to map physical interactions between promoters and SEs in mouse ESCs.
• Compared interaction profiles across different pluripotent cell states, including ESCs, epiblast stem cells (EpiSCs), and Nanog-deficient ESCs.

Main Results:

• Demonstrated that SEs form intricate spatial networks, with individual SEs interacting with multiple promoters.
• Observed a significant rewiring of promoter-SE interactions between different pluripotent cell states.
• Found that long-range promoter-SE interactions are more common in ESCs compared to EpiSCs or Nanog-deficient ESCs.

Conclusions:

• Super-enhancers establish cell-type-specific interaction networks with promoters that are essential for regulating gene expression.
• These interaction networks exhibit plasticity and undergo rewiring during cell state transitions.
• The maintenance of promoter-SE interactions is partially dependent on core transcription factors, offering critical insights into the gene regulatory architecture of pluripotent cells.