Enhancer-promoter communication: hubs or loops?

Abstract

There has been a sea change in our view of transcription regulation during the past decade (Fukaya et al., 2016, Lim et al., 2018, Hnisz et al., 2017 [3], Liu et al., 2018 [4], Kato et al., 2012). Classical models of enhancer-promoter interactions and the stepwise assembly of individual RNA Polymerase II (Pol II) complexes have given way to the realization that active transcription foci contain clusters-hubs-of transcriptional activators and Pol II. Here we summarize recent findings pointing to the occurrence of transcription hubs and the implications of such hubs on the regulation of gene activity.

Figure 1

(A) Formation of transcription hub as a possible mechanism for gene regulation. When transcription is active, TFs, Pol II, Mediators and other transcription machineries can form multivalent phase-separated condensates (or clusters) that facilitate enhancer-promoter interactions for transcriptional initiation. (B) A schematic of the visualization of enhancer (blue), gene 1 (green), and gene 2 (red) loci shown in (A) when transcription is OFF and ON. The distance between enhancer and the target promoter is not as close as expected (200~400 nm), possibly due to large size of higher order associations of transcription complexes. (C) A representative transcriptional trajectory from two linked reporter genes regulated by a single enhancer. The occurrence of coordinate busting can be explained by the transcription hub model. Data is obtained from [1].