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

In this Perspective, Karr et al. 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. 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.

Automated summary

This Perspective presents a new model for understanding how distal cis-regulatory elements communicate with promoters, diverging from the traditional enhancer-promoter looping paradigm. The model focuses on the coactivator p300 and offers a synthesis of the current literature to support its plausibility.