双链DNA微阵列也称为蛋白结合微阵列, 是高通量检测分析DNA结合蛋白(如转录因子)与大量DNA分子相互作用的一种重要技术。它将大量双链DNA分子固定在特定的固相支持物(如玻片)上, 与待测蛋白相互作用, 用以确定转录因子的DNA结合亲和性、特异性及序列偏好性。近年来, 该技术在快速表征大量转录因子的DNA特异性、绘制转录因子DNA结合谱、鉴定转录因子DNA结合位点和靶基因、识别转录因子家族内不同成员及其二聚体的细微DNA结合差异、考察辅助因子对转录因子DNA结合特异性影响等方面展现了其重要的应用价值。文章对双链DNA微阵列的原理、技术及应用进行了综述。
Double-stranded DNA (dsDNA) microarray, also known as protein binding microarray (PBM), is an important technique that can be used to assay the interaction of DNA-binding protein (such as transcription factor, TF) with vast amount of DNA molecules in high-throughput format. This technique immobilizes large amount of various dsDNA molecules on the surface of a solid support (such as glass slide) for detecting the binding interaction of a DNA-binding protein with all of the immobilized dsDNA molecules, and thus determining the DNA-binding affinity, specificity and preference of TFs. In recent years, this technique has demonstrated its valuable applications in several aspects, including rapidly characterizing DNA-binding specificity of large number of TFs, building DNA-binding profiles of TFs, identifying DNA-binding sites and target genes of TFs, discriminating the subtle DNA-binding preferences of members and their dimmers of a TF family, and examining the effects of a cofactor on the DNA-binding specificity of TFs. This paper reviews the principal, techniques, and applications of dsDNA microarray.
[1] Busser BW, Bulyk ML, Michelson AM. Toward a systems-level understanding of developmental regulatory networks. Curr Opin Genet Dev, 2008, 18(6): 521-529.
[2] Mukherjee S, Berger MF, Jona G, Wang XS, Muzzey D, Snyder M, Young RA, Bulyk ML. Rapid analysis of the DNA-binding specificities of transcription factors with DNA microarrays. Nat Genet, 2004, 36(12): 1331-1339.
[3] Messina DN, Glasscock J, Gish W, Lovett M. An ORFeome-based analysis of human transcription factor genes and the construction of a microarray to interrogate their expression. Genome Res, 2004, 14(10B): 2041-2047.
[4] Lee AP, Yang YC, Brenner S, Venkatesh B. TFCONES: a database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements. BMC Genomics, 2007, 8: 441.
[5] Brivanlou AH, Darnell JE Jr. Signal transduction and the control of gene expression. Science, 2002, 295(5556): 813-818.
[6] Schröder A, Eichner J, Supper J, Wanke D, Henneges C, Zell A. Predicting DNA-binding specificities of eukaryotic transcription factors. PLoS One, 2010, 5(11): e13876.
[7] Bulyk ML, Gentalen E, Lockhart DJ, Church GM. Quantifying DNA-protein interactions by double-stranded DNA arrays. Nat Biotechnol, 1999, 17(6): 573-577.
[8] Bulyk ML. Protein binding microarrays for the characterization of DNA-protein interactions. Adv Biochem Eng Biotechnol, 2007, 104: 65-85.
[9] Stormo GD, Zhao Y. Determining the specificity of protein- DNA interactions. Nat Rev Genet, 2010, 11(11): 751-760.
[10] Bulyk ML, Huang XH, Choo Y, Church GM. Exploring the DNA-binding specificities of zinc fingers with DNA microarrays. Proc Natl Acad Sci USA, 2001, 98(13): 7158-7163.
[11] Wang JK, Li TX, Lu ZH. A method for fabricating uni- dsDNA microarray chip for analyzing DNA-binding proteins. J Biochem Biophys Methods, 2005, 63(2): 100-110.
[12] Wang JK, Bai YF, Li TX, Lu ZH. DNA microarrays with unimolecular hairpin double-stranded DNA probes: fabrication and exploration of sequence-specific DNA/ protein interactions. J Biochem Biophys Methods, 2003, 55(3): 215-232.
[13] Wang JK, Li TX, Bai YF, Zhu YZ, Lu ZH. Fabrication of unimolecular double-stranded DNA microarrays on solid surfaces for probing DNA-protein/drug interactions. Molecules, 2003, 8(1): 153-168.
[14] Warren CL, Kratochvil NCS, Hauschild KE, Foister S, Brezinski ML, Dervan PB, Phillips GN Jr, Ansari AZ. Defining the sequence-recognition profile of DNA-binding molecules. Proc Natl Acad Sci USA, 2006, 103(4): 867-872.
[15] Puckett JW, Muzikar KA, Tietjen J, Warren CL, Ansari AZ, Dervan PB. Quantitative microarray profiling of DNA-binding molecules. J Am Chem Soc, 2007, 129(40): 12310-12319.
[16] Kim MJ, Lee TH, Pahk YM, Kim YH, Park HM, Choi YD, Nahm BH, Kim YK. Quadruple 9-mer-based protein binding microarray with DsRed fusion protein. BMC Mol Biol, 2009, 10: 91.
[17] Alleyne TM, Peña-Castillo L, Badis G, Talukder S, Berger MF, Gehrke AR, Philippakis AA, Bulyk ML, Morris QD, Hughes TR. Predicting the binding preference of transcription factors to individual DNA k-mers. Bioinformatics, 2009, 25(8): 1012-1018.
[18] Zhu C, Byers KJRP, McCord RP, Shi ZW, Berger MF, Newburger DE, Saulrieta K, Smith Z, Shah MV, Radhakrishnan M, Philippakis AA, Hu YH, De Masi F, Pacek M, Rolfs A, Murthy T, Labaer J, Bulyk ML. High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res, 2009, 19(4): 556-566.
[19] Berger MF, Bulyk ML. Universal protein-binding microarrays for the comprehensive characterization of the DNA-binding specificities of transcription factors. Nat Protoc, 2009, 4(3): 393-411.
[20] Jolma A, Taipale J. Methods for analysis of transcription factor DNA-binding specificity in vitro. Subcell Biochem, 2011, 52: 155-17
