Cohesin is required for long-range enhancer action at the Shh locus

Lauren Kane, Iain Williamson, Ilya Flyamer, Yatendra Kumar, Robert E. Hill, Laura A. Lettice, Wendy A Bickmore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The regulatory landscapes of developmental genes in mammals can be complex, with enhancers spread over many hundreds of kilobases. It has been suggested that three-dimensional genome organization, particularly topologically associating domains formed by cohesin-mediated loop extrusion, is important for enhancers to act over such large genomic distances. By coupling acute protein degradation with synthetic activation by targeted transcription factor recruitment, here we show that cohesin, but not CTCF, is required for activation of the target gene Shh by distant enhancers in mouse embryonic stem cells. Cohesin is not required for activation directly at the promoter or by an enhancer located closer to the Shh gene. Our findings support the hypothesis that chromatin compaction via cohesin-mediated loop extrusion allows for genes to be activated by enhancers that are located many hundreds of kilobases away in the linear genome and suggests that cohesin is dispensable for enhancers located more proximally.

Original languageEnglish
Pages (from-to)891-897
JournalNature Structural & Molecular Biology
Issue number9
Publication statusPublished - 12 Sept 2022

Keywords / Materials (for Non-textual outputs)

  • Animals
  • CCCTC-Binding Factor/genetics
  • Cell Cycle Proteins/genetics
  • Chromatin/genetics
  • Chromosomal Proteins, Non-Histone/genetics
  • Enhancer Elements, Genetic/genetics
  • Hedgehog Proteins/genetics
  • Mammals/genetics
  • Mice
  • Transcription Factors/metabolism


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