Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner. Mechanistically, this is dependent on SAF-A’s AAA+ATPase domain, which mediates cycles of protein oligomerization with caRNAs, in response to ATP binding and hydrolysis. SAF-A oligomerization decompacts large-scale chromatin structure while SAF-A loss or monomerization promotes aberrant chromosome folding and accumulation of genome damage. Our results show that SAF-A and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes large-scale chromosome structures and protects the genome from instability.

中文翻译：

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SAF-A通过与染色质相关的RNA寡聚化来调节相间染色体结构。

较高等的真核染色体被组织成拓扑受约束的功能域。然而，维持这些复杂的相间染色质结构所需的分子机制尚不清楚。假设建立了一个稳定的核组织基础矩阵，但是随着染色质行为的更多动态模型逐渐流行，这一想法被放弃了。在这里，我们报告支架附着因子A（SAF-A），最初被确定为结构核蛋白，通过其RGG结构域与染色质相关的RNA（caRNA）相互作用，以转录依赖性方式调节人间相染色质结构。从机理上讲，这取决于SAF-A的AAA + ATPase结构域，该结构域响应ATP结合和水解作用，介导caRNA与蛋白质寡聚化的循环。SAF-A寡聚化分解了大规模的染色质结构，而SAF-A的丢失或单体化促进了异常的染色体折叠和基因组损伤的积累。我们的结果表明，SAF-A和caRNA形成了动态的，转录响应的染色质网格，可以组织大规模的染色体结构并保护基因组免受不稳定的影响。