The Nuclear Matrix Regulates Gene Induction By Maintaining the Chromatin-Speckle Association and Compartmentalization [Hi-C]

Emerging evidence reveals the critical role of the nuclear RNA-protein meshwork complex, termed nuclear matrix, in stabilizing chromatin architecture. While chromatin associates with transcriptional machinery within nuclear bodies to regulate gene expression through hierarchical architecture formation, how the nuclear matrix mediates chromatin-nuclear body associations and their spatial organization remains unclear. Here, we demonstrate that depletion of nuclear matrix factor SAF-A leads to genome-wide chromatin compaction and enhanced chromatin-speckle associations. Using super-resolution imaging and genomic analyses, we show that these chromatin organizational changes alter the inducibility of speckle-associated genes. Mechanistically, we reveal that nuclear matrix exhibits a layered spatial distribution, forming distinct compartments with RNA polymerase II clusters and chromatin in the perispeckle region. Our findings demonstrate that nuclear matrix maintains chromatin architecture and regulates gene expression through spatial coupling with nuclear bodies, providing new insights into the hierarchical organization of nuclear structure-function relationships. Overall design: Hi-C profiling of HCT116 osTIR1(F74G) SAF-A-mAID-Halo TetOn-SAF-A(WT or RBD del) cells and dox treatment for 24hr followed by acute depletion with 5-Ph-IAA treatment for 3hr and 12hr.