Nuclear speckles as a key regulator for the 3D genome organization [HiC]

The nuclei of eukaryotes contain various higher-order chromatin architectures and nuclear bodies (NBs), which are critical for proper nuclear functions. By using mouse hepatocytes as the model, we knocked-down SRRM2, a core protein component scaffolding NSs, and performed Hi-C experiments to examine genome-wide chromatin interactions. We found that Srrm2 depletion disrupted the NSs and changes expression of about 1,000 genes. The intra-chromosomal interactions were decreased in type A (active) compartments and increased in type B (repressive) compartments. Furthermore, upon Srrm2 knockdown, the insulation of TADs was decreased specifically in active compartments, and the most significant reduction was found in the A1 sub-compartments. We showed that disruption of NSs by Srrm2 knockdown led to a global decrease of chromatin interactions in active compartments, indicating critical functions of NSs in the organization of the 3D genome. HiC data in Control and SRRM2 KD AML12 cells.