Cohesin is Required for Long-range Enhancer Action at the Shh Locus

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2022 Sep 13

PMID 36097291

Authors

Lauren Kane

Iain Williamson

Ilya M Flyamer

Yatendra Kumar

Robert E Hill

Laura A Lettice

Wendy A Bickmore

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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