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

   June 14th, 2021 at 5:34pm



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. These maps reveal several characteristics of caRNA distribution. caRNA is preferentially associated with its transcription site and up to several megabases of flanking genomic sequence. Furthermore, topologically associating domain (TAD) boundaries insulate RNA-DNA contacts. Abolishment or creation of a TAD boundary by genomic editing changed the boundarys ability to insulate RNA-DNA contacts, demonstrating an impact of the 3D genome structure on the distribution of caRNA. Conversely, depletion of caRNA weakens TAD boundaries. We characterize caRNA based on their target genomic sequence into loop-anchor-associated RNA and those associated with any genomic sequence between loop anchors (between-anchor caRNA). Between-anchor caRNA suppresses chromatin loops, especially those with convergent CTCF binding sites in their loop anchors. These data suggest the indispensable roles of caRNA in the 3D genome organization.


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






September 7th, 2022