Detection and Application of 5-Formylcytosine and 5-Formyluracil in DNA
Detection and Application of 5-Formylcytosine and 5-Formyluracil in DNA
复制标题
DNA中5-甲酰胞嘧啶和5-甲酰尿嘧啶的检测及应用
DOI：
10.1021/acs.accounts.8b00543
复制
发表时间：
2019
影响因子：
18.3
通讯作者：
Zhou Xiang
中科院分区：
文献类型：
--
作者：
Wang Yafen;Zhang Xiong;Zou Guangrong;Peng Shuang;Liu Chaoxing;Zhou Xiang
概述核酸含有多种不同的碱基修饰，例如胞嘧啶第五位的修饰，这是最重要的表观遗传修饰之一。核酸表观遗传学介导多种生物过程，包括胚胎发育和基因调控、基因组印记、分化和 X 染色体失活。此外，修饰水平可以在不同的组织中异常表达，这可以指示不同的肿瘤发作和癌变。因此，修饰核碱基的分析可能有助于理解表观遗传修饰相关的生物过程以及修饰核碱基模式与临床诊断和治疗疾病状态的相关性。除5-甲基胞嘧啶外，5-羟甲基胞嘧啶、5-甲酰基胞嘧啶和5-羧基胞嘧啶在生物体中含量较低，但仍然是极其重要的化学修饰，还存在5-羟基尿嘧啶和5-甲酰尿嘧啶化合物。 5-甲酰尿嘧啶存在于噬菌体、原核生物和哺乳动物细胞中。某些癌组织中的5-甲酰尿嘧啶含量高于肿瘤邻近的正常组织。不同细胞组织中5-甲酰尿嘧啶的含量可能具有细胞类型特异性。随着化学工具的不断使用，新的检测技术极大地推进了天然嘧啶修饰的研究。这些修饰动态调节真核生物和原核生物中的基因表达，并为疾病的发生提供机制见解。天然嘧啶修饰不仅充当 DNA 去甲基化或氧化损伤产物的中间体，而且充当基因表达的调节剂。因此，开发更有效的化学工具将有助于我们更好地了解天然嘧啶修饰在体内的动态变化。在本篇文章中，我们总结了近年来检测5-甲酰嘧啶（5-甲酰胞嘧啶和5-甲酰尿嘧啶）的先进技术，并强调了它们作为生物标志物在生物医学应用中的巨大潜力。针对表观遗传修饰检测的迫切性，我们课题组近年来开发了一系列5-甲酰嘧啶定性和定量分析方法，旨在促进这些表观遗传修饰的准确检测和定位。通过构建探针，可以选择性地标记5-甲酰基嘧啶。使用质谱法，可以量化表观遗传修饰。经过特定条件下的处理，5-甲酰胞嘧啶可以在单碱基分辨率下被识别。通过这个帐户，我们期望为化学和生物学研究人员提供一些见解，以解开5-甲酰嘧啶相关生物过程中涉及的复杂机制，并激发来自材料、生物、医学和化学不同领域的更多合作研究兴趣，以促进表观遗传学在肿瘤诊断和治疗中的转化研究。
ConspectusNucleic acids contain a variety of different base modifications, such as decoration at the fifth position of cytosine, which is one of the most important epigenetic modifications. Nucleic acid epigenetics mediate a wide variety of biological processes, including embryonic development and gene regulation, genomic imprinting, differentiation, and X-chromosome inactivation. Furthermore, the modification level can be aberrantly expressed in distinct sets of tissue that can indicate different tumor onsets and canceration. Thus, the analysis of modified nucleobases may contribute to the understanding of epigenetic modification-related biological processes and the correlation of modified nucleobase patterns with disease states for clinical diagnosis and treatment. In addition to 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine are found in organisms at a low content but are nevertheless extremely important chemical modifications, and 5-hydroxyuracil and 5-formyluracil compounds are also present. 5-Formyluracil is found in bacteriophages, prokaryotes, and mammalian cells. The 5-formyluracil content is higher in certain cancer tissues than in the normal tissues adjacent to the tumor. The content of 5-formyluracil in different cell tissues may have cell type specificity.With the continuous use of chemical tools, new detection technologies have greatly advanced the research on natural pyrimidine modifications. These modifications dynamically regulate the gene expression in eukaryotes and prokaryotes and provide mechanistic insights into the occurrence of diseases. Natural pyrimidine modifications act not only as intermediates for DNA demethylation or oxidative damage products but also as modulators of gene expression. Therefore, the development of more effective chemical tools will help us better understand the dynamic changes of natural pyrimidine modificationsin vivo.In this Account, we summarize the recent advanced techniques for the detection of 5-formylpyrimidine (5-formylcytosine and 5-formyluracil) and highlight their great potential as biomarkers in biomedical applications. Focusing on the great urgency for the detection of epigenetic modifications, our group developed a series of methods for the qualitative and quantitative analysis of 5-formylpyrimidine in the past few years, aiming at facilitating the accurate detection and mapping of these epigenetic modifications. By the construction of probes, 5-formylpyrimidine can be selectively labeled. Using mass spectrometry, the epigenetic modifications can be quantified. Upon treatment under specific conditions, 5-formylcytosine can be recognized at single-base resolution.With this Account, we anticipate providing chemical and biological researchers with some insight to unlock the complex mechanism involved in 5-formylpyrimidine-related biological processes and stimulate more collaborative research interests from the different fields of materials, biological, medicine, and chemistry to promote the translational research of epigenetics in tumor diagnosis and treatment.