Phase Separation and Transcription Regulation: Are Super-Enhancers and Locus Control Regions Primary Sites of Transcription Complex Assembly?

Aishwarya Gurumurthy,Eliot M Gunn,Yong Shen,Jörg Bungert

doi:10.1002/bies.201800164

Aishwarya Gurumurthy, Eliot M Gunn + Show 2 more

Open Access

https://doi.org/10.1002/bies.201800164

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Journal: BioEssays	Publication Date: Nov 30, 2018
Citations: 40	License type: CC BY 4.0

Affiliation: University of Florida, University of Florida Health

Abstract

It is proposed that the multiple enhancer elements associated with locus control regions and super-enhancers recruit RNA polymerase II and efficiently assemble elongation competent transcription complexes that are transferred to target genes by transcription termination and transient looping mechanisms. It is well established that transcription complexes are recruited not only to promoters but also to enhancers, where they generate enhancer RNAs. Transcription at enhancers is unstable and frequently aborted. Furthermore, the Integrator and WD-domain containing protein 82 mediate transcription termination at enhancers. Abortion and termination of transcription at the multiple enhancers of locus control regions and super-enhancers provide a large pool of elongation competent transcription complexes. These are efficiently captured by strong basal promoter elements at target genes during transient looping interactions.

Highlights

RNA polymerase II (Pol II) is efficiently recruited to individual enhancer elements of locus control regions (LCRs) and super-enhancers (SEs), and initiates bi-directional transcription
Phase separation at LCRs and SEs facilitates assembly of elongation competent transcription complexes.—Recent studies demonstrate that high concentrations of Pol II C-terminal domain (CTD) and Mediator, through multivalent interactions, form condensates leading to the formation of liquid droplets, a process referred to as phase separation [49,63–66]
Accumulating evidence suggests that SEs and LCRs efficiently recruit and assemble elongation competent transcription complexes

Summary

Graphical Abstract

Super-enhancers and locus control regions recruit Mediator and RNA Polymerase II transcription complexes, which form phase separated domains. Termination at the super-enhancers provides a large pool of transcription competent Pol II that is efficiently captured by strong basal promoter elements at the target genes. Mediator; phase separation; RNA polymerase II; super-enhancer; transcription regulation

Introduction

Enhancers and Promoters recruit transcription complexes and initiate transcription

LCRs and SEs are centers of efficient Pol II recruitment and transcription complex assembly

Mediator recruits the unphosphorylated form of

Elongation competent

The human β-globin LCR serves as a center for transcription complex assembly—The

Conclusion and Outlook