current
TCPA: There is a clear relationship between nuclear genome organization and the regulation of gene expression, and a great deal of effort has been dedicated to defining the effects of genome architecture on gene activity. Herein, we propose to complement this work by approaching the relationship from the other direction. We will ask: how does nascent RNA synthesis from enhancers and promoters impact genome organization? Our specific hypothesis is that nascent RNA plays a central role in stabilizing transient promoter-enhancer contacts that occur within topologically-associated domains (TADs), and thus facilitates the communication between distal cis-regulatory regions. This idea is supported by recent demonstrations that nascent RNA can serve as a platform for the recruitment and retention of transcription factors and epigenetic modifiers. Accordingly, several studies have suggested roles for specific enhancer RNAs in the establishment or maintenance of three-dimensional (3D) enhancer-promoter loops and associated gene activity. However, a full appreciation for the role of nascent RNA synthesis on genome structure will require a more rigorous, coordinated and comprehensive approach than has been carried out to date. We therefore propose a collaborative project within the framework of the 4D Nucleome network to address how enhancer and gene transcription impact chromosome organization.