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[间期细胞核中管家基因的空间组织]

[Spatial organization of house-keeping genes in interphase nuclei].

作者信息

Gushchanskaia E S, Artemov A A, Ul'ianov S V, Penin A A, Logacheva M D, Razin S V, Gavrilov A A

出版信息

Mol Biol (Mosk). 2014 Nov-Dec;48(6):1008-18.

Abstract

Spatial organization of the eukaryotic genome is tightly connected to its functioning. In particular, the interaction of gene promoters with remote enhancer elements in active chromatin hubs, as well as the recruitment of genes to the common transcription factories plays an important role in regulation of gene transcription. Most of works related to the analysis of spatial interaction of genome regulatory elements relies on models of tissue-specific genes. Meanwhile, it remains unclear to which extent the spatial organization of chromosomes is guided by house-keeping genes that are transcribed in most of cell types and outnumber the transcribed tissue-specific genes. To address this question, we used the 4C technique to characterize genome-wide the spatial contacts of the chicken house-keeping genes CARHSP1 and TRAP1 situated on chromosome 14. The promoters of these genes had an increased frequency of interaction with chromosome regions enriched in CpG islands and binding motifs for the ubiquitous transcription factor Sp1, both of which mark promoters of house-keeping genes, and overall with transcriptionally active regions. By contrast, the analysis of interaction of a gene poor region of chromosome 14 revealed no such preferences. The evidence for the interaction of house-keeping gene promoters were also obtained in independent cytological experiments aimed at visualization of non-methylated CpG islands in individual nuclei of human cells, which showed clustering of CpG islands in the nuclear space. Altogether, the results of our work suggest that the interaction of house-keeping genes constitutes an important factor that determines the spatial organization of interphase chromosomes.

摘要

真核生物基因组的空间组织与其功能紧密相连。特别是,基因启动子与活性染色质枢纽中远距离增强子元件的相互作用,以及基因向共同转录工厂的募集,在基因转录调控中发挥着重要作用。大多数与基因组调控元件空间相互作用分析相关的研究都依赖于组织特异性基因模型。与此同时,在大多数细胞类型中都有转录且数量超过转录的组织特异性基因的管家基因在多大程度上指导染色体的空间组织仍不清楚。为了解决这个问题,我们使用4C技术全基因组地表征了位于14号染色体上的鸡管家基因CARHSP1和TRAP1的空间接触。这些基因的启动子与富含CpG岛和普遍存在的转录因子Sp1结合基序的染色体区域的相互作用频率增加,这两者都标记了管家基因的启动子,并且总体上与转录活性区域相互作用。相比之下,对14号染色体基因贫乏区域相互作用的分析没有发现这样的偏好。在旨在可视化人类细胞单个细胞核中未甲基化CpG岛的独立细胞学实验中也获得了管家基因启动子相互作用的证据,该实验显示CpG岛在核空间中聚集。总之,我们的研究结果表明,管家基因的相互作用是决定间期染色体空间组织的一个重要因素。

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