Enhancer Function in the 3D Genome

Abstract

In this review, we consider various aspects of enhancer functioning in the context of the 3D genome. Particular attention is paid to the mechanisms of enhancer-promoter communication and the significance of the spatial juxtaposition of enhancers and promoters in 3D nuclear space. A model of an activator chromatin compartment is substantiated, which provides the possibility of transferring activating factors from an enhancer to a promoter without establishing direct contact between these elements. The mechanisms of selective activation of individual promoters or promoter classes by enhancers are also discussed.

Keywords: 3D genome; chromatin compartment; enhancer-promoter communication; phase separation.

Figure 1

Different mechanisms for establishing enhancer-promoter communication. (A) Transcription factors and components of transcriptional machinery gathered on the enhancer are transferred to the nearby promoter by RNA polymerase II, which performs low-level intergenic transcription. (B) The condensation of proteins bound to DNA between the enhancer and the promoter brings the enhancer closer to the promoter in physical space. (C) The interaction of architectural proteins bound to the enhancer and the promoter leads to the formation of a DNA loop and the juxtaposition of the enhancer and the promoter.

Figure 2

Models illustrating the possibility of approaching the enhancer and promoter through the operation of extrusion complexes. (A) Unidirectional extrusion of the DNA loop by the cohesin complex fixed on the enhancer leads to the movement of the enhancer along the DNA molecule up to the meeting with the target promoter. (B) Bidirectional extrusion of the DNA loop by a cohesin complex loaded between the enhancer and the promoter results in the juxtaposition of the enhancer and the promoter carrying convergent CTCF binding sites. (C) Loading of multiple extrusion complexes between the enhancer and the promoter results in the formation of a rosette of DNA loops and the juxtaposition of the enhancer and the promoter carrying convergent CTCF binding sites.