表观遗传学新标记--5-羟甲基胞嘧啶检测方法的研究进展

doi:10.16288/j.yczz.15-480

遗传 ›› 2016, Vol. 38 ›› Issue (3): 206-216.doi: 10.16288/j.yczz.15-480

表观遗传学新标记--5-羟甲基胞嘧啶检测方法的研究进展

方科, 张凯翔, 王建, 付志猛, 赵湘辉

第四军医大学基础医学部神经生物学教研室暨脑科学协同创新中心,西安710032

收稿日期:2015-11-26 修回日期:2015-12-25 出版日期:2016-03-20 发布日期:2016-03-20
通讯作者: 赵湘辉,博士,副教授,研究方向:神经发育的表观遗传调控. E-mail:xianghuizhao@fmmu.edu.cn
作者简介:方科,本科,临床医学专业.E-mail: fxzbzhyh@foxmail.com
基金资助:
国家自然科学基金(编号:31371077,31571050)和陕西省科学技术研究发展计划项目(编号:2014KJXX-57)资助

Advances on the profiling of 5-hydroxymethylcytosine

Ke Fang, Kaixiang Zhang, Jian Wang, Zhimeng Fu, Xianghui Zhao

Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China

Received:2015-11-26 Revised:2015-12-25 Online:2016-03-20 Published:2016-03-20
Supported by:
Supported by the National Natural Science Foundation of China (Nos; 31371077,31571050) and Shaanxi Science and Technology Research and Development Program (No; 2014KJXX-57)

摘要/Abstract

摘要： 被称为"第六种碱基"的5-羟甲基胞嘧啶(5-hydroxymethylcytosine, 5hmC),广泛分布于多种哺乳动物的组织和细胞中,与胚胎发育,神经系统功能以及肿瘤研究高度相关.与5-甲基胞嘧啶(5-methylcytosine, 5mC)相比,5hmC在组织中含量更低,难以精确的检测.随着研究的深入,5hmC参与的重要生物学作用逐渐被人们发现,同时也促使着5hmC的检测和定量方法不断发展.为了区分5hmC与其他胞嘧啶衍生物,很多利用化学或者酶学修饰实现靶向检测或非靶向富集5hmC的方法应运而生.因此,选择并发展灵敏,准确,可靠的5hmC检测技术对于表观遗传研究至关重要.本文重点综述了近年来发展起来的5hmC检测和测序技术,通过比较分析各种方法的优缺点,为研究人员选择特定合适的方法开展相关研究提供重要的参考.

关键词: 表观遗传学, 5-羟甲基胞嘧啶, 检测方法, 高通量测序

Abstract: 5-hydroxymethylcytosine (5hmC) is a naturally existing component in mammalian genomic DNA and is regarded as the sixth DNA base. Accumulating studies have revealed the essential role of 5hmC in embryonic development, brain function and cancer research. Compared to another well-known cytosine methylation derivate, 5-methylcytosine (5mC), the detection of 5hmC is difficult for its lower lever existing in most tissues. To distinguish 5hmC from other cytosine derivates, the methods using chemical or enzymatic DNA treatment, have been applied in targeted 5hmC detection or non-targeted 5hmC enrichment. Therefore, profiling DNA hydroxymethylcytosine by sensitive, accurate and reliable method is crucial for epigenetic study. This review discusses the principles behind recently developed techniques for 5hmC quantification and mapping. By comparing the advantages and shortcomings of these methods, the general guidelines were provided on how to select appropriate methods for specific experimental contexts.

Key words: epigenetic, hydroxymethylcytosine, profiling, high-throughput sequencing

方科, 张凯翔, 王建, 付志猛, 赵湘辉. 表观遗传学新标记--5-羟甲基胞嘧啶检测方法的研究进展[J]. 遗传, 2016, 38(3): 206-216.

Ke Fang, Kaixiang Zhang, Jian Wang, Zhimeng Fu, Xianghui Zhao. Advances on the profiling of 5-hydroxymethylcytosine[J]. HEREDITAS(Beijing), 2016, 38(3): 206-216.

参考文献

[1] Wyatt GR, Cohen SS. A new pyrimidine base from bacteriophage nucleic acids. Nature , 1952, 170(4338): 1072- 1073.
[2] Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science , 2009, 324(5929): 929-930.
[3] Tahiliani M, Koh KP, Shen YH, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science , 2009, 324(5929): 930-935.
[4] Wu H, Zhang Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev , 2011, 25(23): 2436-2452.
[5] Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development , 2012, 139(11): 1895-1902.
[6] Zhang YX, Gao KR, Yu SY. Progress of research on 5-hydroxymethylcytosine. Hereditas (Beijing) , 2012, 34(5): 509- 518. 张燕霞, 高可润, 禹顺英. 5-羟甲基胞嘧啶的研究进展. 遗传, 2012, 34(5): 509-518.
[7] Jin SG, Jiang Y, Qiu RX, Rauch TA, Wang YS, Schackert G, Krex D, Lu Q, Pfeifer GP. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res , 2011, 71(24): 7360- 7365.
[8] Lian CG, Xu YF, Ceol C, Wu FZ, Larson A, Dresser K, Xu WQ, Tan L, Hu YG, Zhan Q, Lee CW, Hu D, Lian BQ, Kleffel S, Yang YJ, Neiswender J, Khorasani AJ, Fang R, Lezcano C, Duncan LM, Scolyer RA, Thompson JF, Kakavand H, Houvras Y, Zon LI, Mihm MC Jr, Kaiser UB, Schatton T, Woda BA, Murphy GF, Shi YG. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell , 2012, 150(6): 1135-1146.
[9] Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature , 2010, 466(7310): 1129-1133.
[10] Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science , 2011, 333(6047): 1300-1303.
[11] Nestor C, Ruzov A, Meehan RR, Dunican DS. Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA. Biotechniques , 2010, 48(4): 317-319.
[12] Jin SG, Kadam S, Pfeifer GP. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res , 2010, 38(11): e125.
[13] Leoni C, Montagner S, Deho' L, D'Antuono R, De Matteis G, Marzano AV, Merante S, Orlandi EM, Zanotti R, Monticelli S. Reduced DNA methylation and hydroxymethylation in patients with systemic mastocytosis. Eur J Haematol , 2015, 95(6): 566-575.
[14] Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R, Liu XS, Aravind L, Agarwal S, Maciejewski JP, Rao A. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature , 2010, 468(7325): 839-843.
[15] He YF, Li BZ, Li Z, Liu P, Wang Y, Tang QY, Ding JP, Jia YY, Chen ZC, Li L, Sun Y, Li XX, Dai Q, Song CX, Zhang KL, He C, Xu GL. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science , 2011, 333(6047): 1303-1307.
[16] Ruoppolo M, Nitti G, Valsasina B, Malorni A, Marino G, Pucci P. Disulfide isoform intermediates in the reoxidation of recombinant human basic fibroblast growth factor. Biochemistry , 1993, 32(19): 4991-4996.
[17] Thomas B, Akoulitchev AV. Mass spectrometry of RNA. Trends Biochem Sci , 2006, 31(3): 173-181.
[18] Globisch D, Münzel M, Müller M, Michalakis S, Wagner M, Koch S, Brückl T, Biel M, Carell T. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One , 2010, 5(12): e15367.
[19] Le T, Kim KP, Fan GP, Faull KF. A sensitive mass spectrometry method for simultaneous quantification of DNA met

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表观遗传学新标记--5-羟甲基胞嘧啶检测方法的研究进展

Advances on the profiling of 5-hydroxymethylcytosine

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