I-motif DNA structures are formed in the nuclei of human cells

I-motif DNA structures are formed in the nuclei of human cells
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DOI:
10.1038/s41557-018-0046-3
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发表时间:
2018-06-01
期刊:
影响因子:
21.8
通讯作者:
Christ, Daniel
Christ, Daniel
中科院分区:
化学1区
文献类型:
--
作者:
Zeraati, Mahdi;Langley, David B.;Christ, Daniel

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人类基因组功能的基础是遗传信息在标准b型DNA中的主要存储,第二层DNA结构提供调控控制。i基序结构被认为在基因组富含胞嘧啶的区域形成并具有调节功能;然而,到目前为止,这种结构存在的体内证据仍然难以捉摸。在这里,我们报道了一种抗体片段(iMab)的产生和表征,该抗体片段以高选择性和亲和力识别i-motif结构,从而能够检测人类细胞核中的i-motif。我们证明,这种结构的体内形成是细胞周期和pH依赖。此外,我们提供的证据表明,i-motif结构在人类基因组的调控区域形成,包括启动子和端粒区域。我们的研究结果支持i-motif结构在基因组中发挥关键调控作用的观点。
Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.