Three-dimensional organization of chromatin associated RNAs and their role in chromatin architecture in human cells

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 caRNAs 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 caRNAs 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 caRNAs 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 caRNAs multifaced role in regulating 3D chromatin organization and highlight caRNAs ability to modulate chromatin looping.

Authors

Calandrelli R  •  Wen X  •  Nguyen TC  •  Chen C-J  •  Qi Z  •  Chen W  •  Yan Z  •  Wu W  •  Zaleta-Rivera K  •  Hu R  •  Yu M  •  Wang Y  •  Ma J  •  Ren B  •  Zhong S

Link

http://biorxiv.org/lookup/doi/10.1101/2021.06.10.447969