title: Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling.
abstract: 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.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Hu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Akishi
authors.initials: A
authors.lastname: Onishi
authors.forename: Xueping
authors.initials: X
authors.lastname: Yu
authors.forename: Lizhi
authors.initials: L
authors.lastname: Jiang
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lin
authors.forename: Hee-sool
authors.initials: HS
authors.lastname: Rho
authors.forename: Crystal
authors.initials: C
authors.lastname: Woodard
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Jun-Seop
authors.initials: JS
authors.lastname: Jeong
authors.forename: Shunyou
authors.initials: S
authors.lastname: Long
authors.forename: Xiaofei
authors.initials: X
authors.lastname: He
authors.forename: Herschel
authors.initials: H
authors.lastname: Wade
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
mesh_terms: D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1