Abstract
Chromatin-associated RNA (caRNA) is a vital component of the interphase nucleus; yet its distribution and role in the three-dimensional (3D) genome organization and function remain poorly understood. Here, we map caRNA’s spatial distribution on the 3D genome in human embryonic stem cells, fibroblasts, and myelogenous leukemia cells. We find that the relative abundance of trans-acting caRNA reflects the functional nuclear compartmentalization of the 3D genome, and the caRNA’s sequence features are predictive of its spatial localization. We observe extensive caRNA-genome interactions that span several hundred kilobases to several megabases. These caRNA domains correlate with chromatin loops and enhancer-promoter interactions. We report a tradeoff of caRNA’s promotive and suppressive roles to chromatin interactions. As a result, caRNA promotes chromatin interactions outside the anchors of chromatin loops, whereas caRNA exhibits an overall suppressive impact to chromatin interactions between loop anchors. Furthermore, caRNA suppresses chromatin loops’ number and strengths genome-wide, and this suppression depends on electric charge-mediated RNA interactions. These results reveal caRNA’s multifaced role in regulating 3D chromatin organization and highlight caRNA’s ability to modulate chromatin looping.
Competing Interest Statement
The authors have declared no competing interest.
