Enhancer release and retargeting activates disease-susceptibility genes.

ABSTRACT: The functional engagement between an enhancer and its target promoter ensures precise gene transcription¹. Understanding the basis of promoter choice by enhancers has important implications for health and disease. Here we report that functional loss of a preferred promoter can release its partner enhancer to loop to and activate an alternative promoter (or alternative promoters) in the neighbourhood. We refer to this target-switching process as 'enhancer release and retargeting'. Genetic deletion, motif perturbation or mutation, and dCas9-mediated CTCF tethering reveal that promoter choice by an enhancer can be determined by the binding of CTCF at promoters, in a cohesin-dependent manner-consistent with a model of 'enhancer scanning' inside the contact domain. Promoter-associate

SUBMITTER: Oh S 

PROVIDER: S-EPMC11171441 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature