SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.
SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.
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DOI：
10.1016/j.cell.2017.05.029
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发表时间：
2017-06-15
期刊：
影响因子：
64.5
通讯作者：
Gilbert N
中科院分区：
文献类型：
--
作者：
Nozawa RS;Boteva L;Soares DC;Naughton C;Dun AR;Buckle A;Ramsahoye B;Bruton PC;Saleeb RS;Arnedo M;Hill B;Duncan RR;Maciver SK;Gilbert N
高等真核生物染色体被组织成拓扑受限的功能域；然而，维持这些复杂的间期染色质结构所需的分子机制尚不清楚。一个稳定的矩阵支撑核组织的假设，但这个想法被放弃了更多的动态模型的染色质行为变得普遍。在这里，我们报道了支架附着因子A (SAF-A)，最初被鉴定为一种结构核蛋白，通过其RGG结构域与染色质相关rna （caRNAs）相互作用，以转录依赖的方式调节人类间期染色质结构。从机制上讲，这依赖于SAF-A的AAA+ ATP酶结构域，该结构域介导蛋白质与caRNAs的低聚化循环，以响应ATP结合和水解。saa寡聚化会破坏大规模的染色质结构，而saa的缺失或单体化会促进染色体异常折叠和基因组损伤的积累。我们的研究结果表明，SAF-A和caRNAs形成了一个动态的，转录响应的染色质网，组织大规模的染色体结构并保护基因组免受不稳定。SAF-A重塑间期染色体结构转录调节SAF-A与caRNAs的寡聚化SAF-A与caRNAs相互作用形成染色质网染色质结构影响基因组稳定性一个支架蛋白与染色质相关rna相互作用以转录依赖的方式调节人类间期染色质结构。
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. SAF-A remodels interphase chromosome structure Transcription regulates SAF-A oligomerization with caRNAs SAF-A and caRNAs interact to form a chromatin mesh Chromatin structure affects genome stability A scaffolding protein interacts with chromatin-associated RNAs to regulate human interphase chromatin structures in a transcription-dependent manner.