Protein binding microarrays for the characterization of DNA-protein interactions

Protein binding microarrays for the characterization of DNA-protein interactions
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DOI:
10.1007/10_025
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发表时间:
2007-01-01
期刊:
ANALYTICS OF PROTEIN-DNA INTERACTIONS
影响因子:
--
通讯作者:
Bulyk, Martha L.
Bulyk, Martha L.
中科院分区:
其他
文献类型:
--
作者:
Bulyk, Martha L.

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许多重要的细胞过程,如转录调控、重组、复制、修复和DNA修饰,都是由DNA结合蛋白完成的。特别感兴趣的是转录因子(TF),其通过其与DNA结合位点的序列特异性相互作用,以正常细胞生长和分化以及对环境刺激的响应所需的方式调节基因表达。尽管它们很重要,但大多数DNA结合蛋白的DNA结合特异性仍然未知,因为旨在鉴定DNA-蛋白质相互作用的现有技术很费力,可扩展性不高,或者需要有限的生物试剂。最近,一种新的基于DNA微阵列的技术,称为蛋白质结合微阵列(PBM),已被开发出来,允许快速,高通量表征的体外DNA结合位点序列特异性的TF,其他DNA结合蛋白,或合成化合物。结合基因注释数据,比较序列分析和基因表达谱分析,PBM的DNA结合位点数据,可以用来预测哪些基因是由一个给定的TF调节,什么功能是一个给定的TF和它的预测靶基因,以及如何TF可能适合细胞的转录调控网络。
A number of important cellular processes, such as transcriptional regulation, recombination, replication, repair, and DNA modification, are performed by DNA binding proteins. Of particular interest are transcription factors (TFs) which, through their sequence-specific interactions with DNA binding sites, modulate gene expression in a manner required for normal cellular growth and differentiation, and also for response to environmental stimuli. Despite their importance, the DNA binding specificities of most DNA binding proteins still remain unknown, since prior technologies aimed at identifying DNA-protein interactions have been laborious, not highly scalable, or have required limiting biological reagents. Recently a new DNA microarray-based technology, termed protein binding microarrays (PBMs), has been developed that allows rapid, high-throughput characterization of the in vitro DNA binding site sequence specificities of TFs, other DNA binding proteins, or synthetic compounds. DNA binding site data from PBMs combined with gene annotation data, comparative sequence analysis, and gene expression profiling, can be used to predict what genes are regulated by a given TF, what the functions are of a given TF and its predicted target genes, and how that TF may fit into the cell's transcriptional regulatory network.