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Identifying Readers for (hydroxy)methylated DNA Using Quantitative Interaction Proteomics: Advances and Challenges Ahead.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2019-12-19 , DOI: 10.1016/j.jmb.2019.12.014
Velin Marita Sequeira 1 , Michiel Vermeulen 1
Affiliation  

DNA methylation is an epigenetic modification, which regulates gene expression during cellular differentiation. This important function is thought to be carried out by transcriptional regulators, which are "readers" and effectors of this mark. In recent years, quantitative mass spectrometry-based interaction proteomics technology has emerged as a powerful tool to identify readers for methylated and unmethylated DNA in different cellular contexts. Furthermore, recent technology enables proteome-wide quantification of absolute affinities between proteins and methylated and unmethylated DNA in the context of crude nuclear extracts. Finally, recently developed locus-specific interaction proteomics approaches and modifications thereof facilitate an unbiased proteome characterization of methylated and unmethylated genomic loci in vivo. We summarize these recent findings in this review, and we argue that the integration of all these technologies, with also genomic sequencing-based approaches, will eventually result in a more detailed understanding of the link between DNA methylation and the regulation of transcription in health and disease.

中文翻译:

使用定量相互作用蛋白质组学识别(羟基)甲基化 DNA 的读者:未来的进展和挑战。

DNA甲基化是一种表观遗传修饰,在细胞分化过程中调节基因表达。这一重要功能被认为是由转录调节因子执行的,转录调节因子是该标记的“阅读器”和效应器。近年来,基于定量质谱的相互作用蛋白质组学技术已成为识别不同细胞环境中甲基化和未甲基化 DNA 读者的强大工具。此外,最近的技术能够在粗核提取物的背景下对蛋白质与甲基化和未甲基化 DNA 之间的绝对亲和力进行蛋白质组范围的量化。最后,最近开发的位点特异性相互作用蛋白质组学方法及其修改促进了体内甲基化和未甲基化基因组位点的无偏蛋白质组表征。
更新日期:2019-12-19
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