西亚试剂：Profiling the Human Protein-DNA Interactome Reveals ERK2 as

Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling

Shaohui Hu1, 4, 9, Zhi Xie2, 9, Akishi Onishi3, 4, 5, Xueping Yu2, Lizhi Jiang3, 4, 5, Jimmy Lin6, Hee-sool Rho1, 4, Crystal Woodard1, 4, Hong Wang3, 4, 5, Jun-Seop Jeong1, 4, Shunyou Long4, Xiaofei He1, 4, Herschel Wade7, Seth Blackshaw2, 3, 4, 5, ,  , Jiang Qian2, 8, ,   and Heng Zhu1, 4, 8, , 

1 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4 The Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5 Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
6 Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
7 Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
8 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

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.

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