Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Sep 9

PMID 31494034

Citations 170

Authors

Nezha S Benabdallah

Iain Williamson

Robert S Illingworth

Lauren Kane

Shelagh Boyle

Dipta Sengupta

Graeme R Grimes

Pierre Therizols

Wendy A Bickmore

Affiliations

Soon will be listed here.

Abstract

Enhancers can regulate the promoters of their target genes over very large genomic distances. It is widely assumed that mechanisms of enhancer action involve the reorganization of three-dimensional chromatin architecture, but this is poorly understood. The predominant model involves physical enhancer-promoter interaction by looping out the intervening chromatin. However, studying the enhancer-driven activation of the Sonic hedgehog gene (Shh), we have identified a change in chromosome conformation that is incompatible with this simple looping model. Using super-resolution 3D-FISH and chromosome conformation capture, we observe a decreased spatial proximity between Shh and its enhancers during the differentiation of embryonic stem cells to neural progenitors. We show that this can be recapitulated by synthetic enhancer activation, is impeded by chromatin-bound proteins located between the enhancer and the promoter, and appears to involve the catalytic activity of poly (ADP-ribose) polymerase. Our data suggest that models of enhancer-promoter communication need to encompass chromatin conformations other than looping.

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