Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories.
Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories.
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DOI：
10.1007/s00018-013-1465-3
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Trajanoski Z
中科院分区：
文献类型：
--
作者：
Rieder D;Ploner C;Krogsdam AM;Stocker G;Fischer M;Scheideler M;Dani C;Amri EZ;Müller WG;McNally JG;Trajanoski Z
染色体上分离的、共表达的基因可以在空间上接近，但关于这种核组织是如何实现的仍然存在争议。提出的机制包括全球基因组组织、染色体区域的优先定位或各种核体的基因-基因共享。为了研究这个问题，我们选择了一组在人类多能干细胞分化时共表达的基因。我们应用了一种新的多维分析方法，揭示了在基因表达之前，这些基因在细胞核中的相对位置是保守的。通过干细胞分化和伴随基因的表达，我们发现共表达的基因更紧密地联系在一起。此外，我们发现，在相同的1-μm直径邻域中的基因要么与相同的剪接斑点相关，要么在较小程度上与相同的转录工厂相关。丝氨酸-精氨酸(SR)蛋白激酶cdc2样激酶Clk2的过表达导致斑点的扩散导致共享社区的基因数量显著下降。我们定量地证明，散斑和工厂共享的频率可以通过假设在由基因表达之前存在的原始全局基因定位所定义的限制子体积内随机选择核体来解释。我们的结论是，这些基因的空间组织是一个两步过程，在这个过程中，转录诱导的与核体的关联增强和提炼了一个预先存在的全球组织。
Chromosomally separated, co-expressed genes can be in spatial proximity, but there is still debate about how this nuclear organization is achieved. Proposed mechanisms include global genome organization, preferential positioning of chromosome territories, or gene–gene sharing of various nuclear bodies. To investigate this question, we selected a set of genes that were co-expressed upon differentiation of human multipotent stem cells. We applied a novel multi-dimensional analysis procedure which revealed that prior to gene expression, the relative position of these genes was conserved in nuclei. Upon stem cell differentiation and concomitant gene expression, we found that co-expressed genes were closer together. In addition, we found that genes in the same 1-μm—diameter neighborhood associated with either the same splicing speckle or to a lesser extent with the same transcription factory. Dispersal of speckles by overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2 led to a significant drop in the number of genes in shared neighborhoods. We demonstrate quantitatively that the frequencies of speckle and factory sharing can be explained by assuming stochastic selection of a nuclear body within a restricted sub-volume defined by the original global gene positioning present prior to gene expression. We conclude that the spatial organization of these genes is a two-step process in which transcription-induced association with nuclear bodies enhances and refines a pre-existing global organization.
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在鱼类实验中保存大规模染色质结构。
影响因子：
1.6
作者：
Hepperger, Claudia;Otten, Simone;von Hase, Johann;Dietzel, Steffen
通讯作者：
Dietzel, Steffen
影响因子：
9.8
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1.6
作者：
Küpper K;Kölbl A;Biener D;Dittrich S;von Hase J;Thormeyer T;Fiegler H;Carter NP;Speicher MR;Cremer T;Cremer M
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Cremer M
影响因子：
9.8
作者：
Ferrai C;Xie SQ;Luraghi P;Munari D;Ramirez F;Branco MR;Pombo A;Crippa MP
通讯作者：
Crippa MP
影响因子：
3.7
作者：
Duncan, PI;Stojdl, DF;Bell, JC
通讯作者：
Bell, JC