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

• Published in: BioEssays Vol. 41; no. 1; pp. e1800164 - n/a
• Main Authors: Gurumurthy, Aishwarya, Shen, Yong, Gunn, Eliot M., Bungert, Jörg
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-01-2019
• Subjects: beta-Globins - genetics; DNA-directed RNA polymerase; Elongation; Enhancer Elements, Genetic; Enhancers; Gene Expression Regulation; Gene regulation; Genes; Humans; Loci; Locus Control Region; mediators; Phase separation; Proteins; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA Polymerase II - metabolism; super‐enhancer; Transcription elongation; transcription regulation; Transcription termination; Transcription, Genetic; transcription regulation; phase separation; mediators; RNA polymerase II; super-enhancer
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201800164

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.
Super‐enhancers and locus control regions recruit Mediator and RNA Polymerase II transcription complexes, which form phase separated domains. It is proposed that transcription abortion and 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.