Large-scale mapping of positional changes of hypoxia-responsive genes upon activation.
Large-scale mapping of positional changes of hypoxia-responsive genes upon activation.
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DOI：
10.1091/mbc.e21-11-0593
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发表时间：
2022-07-01
影响因子：
3.3
通讯作者：
Misteli, Tom
中科院分区：
文献类型：
--
作者：
Nakayama, Koh;Shachar, Sigal;Finn, Elizabeth H.;Sato, Hiroyuki;Hirakawa, Akihiro;Misteli, Tom
染色体结构和核组织是基因表达调控的重要因素。基因的转录受到局部和全局染色体特征的影响，如染色质凝集状态。基因在细胞核中的3D位置与其活性之间的关系还不是很清楚。在这里，我们使用高通量成像对近100个低氧反应基因的空间位置进行大规模分析，以确定它们的位置和活动状态是否相关。径向距离分析表明，依赖于低氧诱导因子(HIF)和CREB的低氧反应基因大多位于细胞核的中间区域，其中一些基因在低氧时改变了它们的径向位置。对HIF靶基因子集之间的相对距离的分析表明，一些基因对在低氧处理时改变了它们彼此的相对位置，表明染色质重排的顺序更高。虽然这些位置的变化是由于目标基因的缺氧激活而发生的，但它们与它们的激活程度无关。这些结果表明，低氧反应基因表达程序的诱导伴随着基因组的空间变化，但径向和相对基因位置与基因活性没有直接关系。
Chromosome structure and nuclear organization are important factors in the regulation of gene expression. Transcription of a gene is influenced by local and global chromosome features such as chromatin condensation status. The relationship between the 3D position of a gene in the nucleus and its activity is less clear. Here we used high-throughput imaging to perform a large-scale analysis of the spatial location of nearly 100 hypoxia-responsive genes to determine whether their location and activity state are correlated. Radial distance analysis demonstrated that the majority of Hypoxia-Inducible Factor (HIF)- and CREB-dependent hypoxia-responsive genes are located in the intermediate region of the nucleus, and some of them changed their radial position in hypoxia. Analysis of the relative distances among a subset of HIF target genes revealed that some gene pairs altered their relative location to each other on hypoxic treatment, suggesting higher-order chromatin rearrangements. While these changes in location occurred in response to hypoxic activation of the target genes, they did not correlate with the extent of their activation. These results suggest that induction of the hypoxia-responsive gene expression program is accompanied by spatial alterations of the genome, but that radial and relative gene positions are not directly related to gene activity.