Nuclei of eukaryotes contain various higher-order chromatin architectures and nuclear bodies (NBs), which are critical for proper nuclear functions. Recent studies showed that active chromatin regions are associated with nuclear speckles (NSs), a type of NBs involved in RNA processing. However, the functional roles of NSs in 3D genome organization remain unclear. 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 changed the expression of 1282 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 occurred in A1 sub-compartments. Interestingly, the change of intra-TAD chromatin interactions upon Srrm2 depletion was not associated with the alteration of gene expression. We show that disruption of NSs by Srrm2 knockdown causes a global decrease in chromatin interactions in active compartments, indicating critical functions of NSs in the organization of the 3D genome.

中文翻译：

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核斑点的破坏减少了活性区室中的染色质相互作用。

真核生物的核包含各种高级染色质结构和核体（NBs），这对于适当的核功能至关重要。最近的研究表明，活跃的染色质区域与核斑点（NSs）相关，NSs是一种参与RNA加工的NBs。然而，尚不清楚NS在3D基因组组织中的功能作用。使用小鼠肝细胞作为模型，我们敲低了SRRM2（一种核心蛋白成分支架NSs），并进行了Hi-C实验以检查全基因组染色质的相互作用。我们发现Srrm2耗竭破坏了NSs，并改变了1282基因的表达。染色体内相互作用在A型（活动）区室中减少，而在B型（抑制性）区室中增加。此外，在击倒Srrm2时，TAD的隔热性在活动隔间中特别降低，而最大的减少发生在A1子隔间中。有趣的是，Srrm2耗尽后，TAD内染色质相互作用的变化与基因表达的改变无关。我们显示，通过Srrm2敲低NS的破坏会导致活动区室中染色质相互作用的整体下降，这表明NS在3D基因组的组织中的关键功能。