Super-enhancer interactomes from single cells link clustering and transcription

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Gene expression regulation involves enhancers and promoters, typically studied pairwise.
• Advanced genome folding techniques reveal multi-way interactions among super-enhancers (SEs) but lack single-cell frequency and transcriptional correlation data.

Approach:

• Utilized multiplexed imaging to map the 3D positions of 376 SEs in thousands of mammalian nuclei.
• Investigated the formation and characteristics of SE associations in single cells.
• Correlated SE community size with transcriptional burst frequency and magnitude.

Key Points:

• SE-SE direct contacts are infrequent in single cells.
• SEs commonly form looser associations termed "communities" (average 4-5 SEs).
• Community assembly is driven by genomic tethers, Pol2 clustering, and nuclear compartmentalization.

Conclusions:

• Larger SE communities correlate with increased frequency and size of transcriptional bursts.
• Findings challenge existing hypotheses on SE clustering's role in transcriptional regulation.
• Provides novel single-cell insights into the SE interactome and gene expression control.