RT Journal Article SR Electronic T1 Topology of gene regulatory compartments relative to the nuclear matrix JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.05.10.491284 DO 10.1101/2022.05.10.491284 A1 Gunhee Park A1 Kwangmin Ryu A1 Junho Lee A1 Geunhee Kim A1 Tae Lim Park A1 Hwanyong Shim A1 YigJi Lee A1 Changyeop Kim A1 Won-Ki Cho YR 2022 UL http://biorxiv.org/content/early/2022/05/10/2022.05.10.491284.abstract AB Inside the nucleus, there are special compartments with characterized functions, some of which are involved in gene expression1. These compartments include transcriptional condensates and nuclear speckles, which contain factors required for transcription and splicing, respectively. While the characteristics of these intranuclear compartments were extensively investigated, spatial relationship between them is yet unclear. Meanwhile, RNA-protein structural network named the nuclear matrix has been observed inside the nucleus and suggested as a framework for the spatial segregation of the intranuclear space2–6. However, concept of the nuclear matrix was not widely accepted due to its lack of in vivo evidence7. Here, we report visualization of the nuclear matrix and intranuclear compartments using super-resolution fluorescence microscopy. We found the nuclear matrix is dynamic in live cells and easily disrupted upon transcription inhibition. Remarkably, we observed an orderly layered distribution of transcriptional condensates and nuclear speckles relative to the nuclear matrix. We also observed a separation of chromosome territories from transcriptional condensates and nuclear speckles by the nuclear matrix. Based on our findings, we propose a topological model for the regulation of transcription across the nuclear matrix.Competing Interest StatementThe authors have declared no competing interest.