Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling.
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.
Hu
Shaohui
S
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Xie
Zhi
Z
Onishi
Akishi
A
Yu
Xueping
X
Jiang
Lizhi
L
Lin
Jimmy
J
Rho
Hee-sool
HS
Woodard
Crystal
C
Wang
Hong
H
Jeong
Jun-Seop
JS
Long
Shunyou
S
He
Xiaofei
X
Wade
Herschel
H
Blackshaw
Seth
S
Qian
Jiang
J
Zhu
Heng
H
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
D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1