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Review
. 2022 Jan 1;36(1-2):7-16.
doi: 10.1101/gad.349160.121. Epub 2021 Dec 30.

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer-promoter communication

Jonathan P Karr  1 , John J Ferrie  1   2 , Robert Tjian  1   2 , Xavier Darzacq  1
Affiliations
Review

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer-promoter communication

Jonathan P Karr et al. Genes Dev. .

Abstract

How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle-one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer-promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.

Keywords: p300; 3D genome; coactivator; enhancer; gene regulation; transcription.

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Figures

Figure 1.
Figure 1.
Mechanisms of enhancer–promoter communication: There are three different ways in which a distal enhancer could regulate a promoter. (1) Stable contact model: A “compound cis-regulatory” element is formed by a stable complex of TFs (tan), coactivators (green), and the transcriptional machinery (gray). (2) Kiss-and-run model: Upon transient contact, enhancer-bound coactivators deposit PTMs at the promoter, and TFs (red) are transferred. (3) Communication by diffusion model: TFs are activated (purple) at the enhancer and diffuse to the promoter.
Figure 2.
Figure 2.
Picturing the enhancer as a point source of acetylated TFs. An unmodified TF (red) contacts an enhancer bearing activated p300 (green) recruited by a dimeric transcription factor (tan). The acetylated transcription factor (purple) departs from the enhancer and is recycled by being rapidly deacetylated in the nucleoplasm by abundant histone deacetylases (blue).
See this image and copyright information in PMC

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