Hu Shaohui, Xie Zhi, Onishi Akishi, Yu Xueping, Jiang Lizhi, Lin Jimmy, Rho Hee-sool, Woodard Crystal, Wang Hong, Jeong Jun-Seop, Long Shunyou, He Xiaofei, Wade Herschel, Blackshaw Seth, Qian Jiang, Zhu Heng
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell. 2009 Oct 30;139(3):610-22. doi: 10.1016/j.cell.2009.08.037.
Protein-DNA interactions (PDIs) mediate a broad range of functions essential for cellular differentiation, function, and survival. However, it is still a daunting task to comprehensively identify and profile sequence-specific PDIs in complex genomes. Here, we have used a combined bioinformatics and protein microarray-based strategy to systematically characterize the human protein-DNA interactome. We identified 17,718 PDIs between 460 DNA motifs predicted to regulate transcription and 4,191 human proteins of various functional classes. Among them, we recovered many known PDIs for transcription factors (TFs). We identified a large number of unanticipated PDIs for known TFs, as well as for previously uncharacterized TFs. We also found that over three hundred unconventional DNA-binding proteins (uDBPs)--which include RNA-binding proteins, mitochondrial proteins, and protein kinases--showed sequence-specific PDIs. One such uDBP, ERK2, acts as a transcriptional repressor for interferon gamma-induced genes, suggesting important biological roles for such proteins.
蛋白质- DNA相互作用（PDIs）介导了一系列对于细胞分化、功能及存活至关重要的功能。然而，在复杂基因组中全面鉴定和描绘序列特异性PDIs仍然是一项艰巨的任务。在此，我们采用了一种结合生物信息学和基于蛋白质微阵列的策略，系统地表征人类蛋白质- DNA相互作用组。我们在预测调控转录的460个DNA基序与4191个不同功能类别的人类蛋白质之间鉴定出17718个PDIs。其中，我们找回了许多转录因子（TFs）的已知PDIs。我们为已知TFs以及先前未表征的TFs鉴定出大量意外的PDIs。我们还发现，三百多种非常规DNA结合蛋白（uDBPs）——包括RNA结合蛋白、线粒体蛋白和蛋白激酶——表现出序列特异性PDIs。其中一种uDBP，ERK2，作为干扰素γ诱导基因的转录抑制因子，表明这类蛋白质具有重要的生物学作用。
