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DNA 序列背景作为正常组织和癌症组织中 CpG 甲基化不稳定性的标志物。

DNA sequence context as a marker of CpG methylation instability in normal and cancer tissues.

机构信息

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Department of Biology, University of Naples Federico II, 80126, Naples, Italy.

出版信息

Sci Rep. 2020 Feb 3;10(1):1721. doi: 10.1038/s41598-020-58331-w.

Abstract

DNA methylation alterations are related to multiple molecular mechanisms. The DNA context of CpG sites plays a crucial role in the maintenance and stability of methylation patterns. The quantitative relationship between DNA composition and DNA methylation has been studied in normal as well as pathological conditions, showing that DNA methylation status is highly dependent on the local sequence context. In this work, we describe this relationship by analyzing the DNA sequence context associated to methylation profiles in both physiological and pathological conditions. In particular, we used DNA motifs to describe methylation stability patterns in normal tissues and aberrant methylation events in cancer lesions. In this manuscript, we show how different groups of DNA sequences can be related to specific epigenetic events, across normal and cancer tissues, and provide a thorough structural and functional characterization of these sequences.

摘要

DNA 甲基化的改变与多种分子机制有关。CpG 位点的 DNA 结构在维持和稳定甲基化模式方面起着关键作用。在正常和病理条件下,已经研究了 DNA 组成与 DNA 甲基化之间的定量关系,表明 DNA 甲基化状态高度依赖于局部序列结构。在这项工作中,我们通过分析生理和病理条件下与甲基化谱相关的 DNA 序列结构来描述这种关系。特别地,我们使用 DNA 基序来描述正常组织中的甲基化稳定性模式和癌症病变中的异常甲基化事件。在本文中,我们展示了不同组的 DNA 序列如何与正常和癌症组织中的特定表观遗传事件相关,并对这些序列进行了全面的结构和功能表征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83fa/6997448/306f2945402b/41598_2020_58331_Fig1_HTML.jpg

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