Human genomic DNA is widely interspersed with i-motif structures.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-08-29 DOI:10.1038/s44318-024-00210-5
Cristian David Peña Martinez, Mahdi Zeraati, Romain Rouet, Ohan Mazigi, Jake Y Henry, Brian Gloss, Jessica A Kretzmann, Cameron W Evans, Emanuela Ruggiero, Irene Zanin, Maja Marušič, Janez Plavec, Sara N Richter, Tracy M Bryan, Nicole M Smith, Marcel E Dinger, Sarah Kummerfeld, Daniel Christ
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Abstract

DNA i-motif structures are formed in the nuclei of human cells and are believed to provide critical genomic regulation. While the existence, abundance, and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescent staining, and more recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA have remained unclear. Here we utilise high-affinity i-motif immunoprecipitation followed by sequencing to map i-motifs in the purified genomic DNA of human MCF7, U2OS and HEK293T cells. Validated by biolayer interferometry and circular dichroism spectroscopy, our approach aimed to identify DNA sequences capable of i-motif formation on a genome-wide scale, revealing that such sequences are widely distributed throughout the human genome and are common in genes upregulated in G0/G1 cell cycle phases. Our findings provide experimental evidence for the widespread formation of i-motif structures in human genomic DNA and a foundational resource for future studies of their genomic, structural, and molecular roles.

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人类基因组 DNA 中广泛存在 i-motif 结构。
DNA i-motif结构在人类细胞核中形成,被认为具有重要的基因组调控作用。虽然免疫荧光染色法以及最近的核磁共振和 CUT&Tag 技术已经证明并研究了 i-motif 结构在人类细胞中的存在、丰度和分布,但这种结构在人类基因组 DNA 中的丰度和分布仍不清楚。在这里,我们利用高亲和力 i-motif 免疫沉淀,然后进行测序,绘制了人类 MCF7、U2OS 和 HEK293T 细胞纯化基因组 DNA 中 i-motif 的图谱。通过生物层干涉测量法和圆二色性光谱法的验证,我们的方法旨在鉴定能够在全基因组范围内形成i-motif的DNA序列,结果发现此类序列广泛分布于人类基因组中,并且常见于在G0/G1细胞周期阶段上调的基因中。我们的发现为 i-motif 结构在人类基因组 DNA 中的广泛形成提供了实验证据,也为今后研究其基因组、结构和分子作用提供了基础资源。
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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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