TY - JOUR
T1 - Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling
AU - Hu, Shaohui
AU - Xie, Zhi
AU - Onishi, Akishi
AU - Yu, Xueping
AU - Jiang, Lizhi
AU - Lin, Jimmy
AU - Rho, Hee-Sool
AU - Woodard, Crystal
AU - Wang, Hong
AU - Jeong, Jun Seop Seop
AU - Long, Shunyou
AU - He, Xiaofei
AU - Wade, Herschel
AU - Blackshaw, Seth
AU - Qian, Jiang
AU - Zhu, Heng
N1 - Funding Information:
We thank Drs. J. Boeke, P. Cole, J. Nathans, G. Seydoux, T. Shimogori, S. Chen, D. Griffin, S. Taverna, J. Pomerantz, and D. Zack for their comments and suggestions. We also thank Drs. K. Dalby, D. Kalvakolanu, and R. Weiner for providing reagents; and D. McClellan for editorial assistance. This work was supported by the National Institutes of Health (GM076102 to H.Z., J.Q., RR020839 to H.Z., NEI Vision Core Grant to J.Q.), a W. M. Keck Foundation Distinguished Young Investigator in Medical Research Award to S.B., a grant from the Ruth and Milton Steinbach Fund to S.B., and a generous gift from Mr. and Mrs. Robert and Clarice Smith.
PY - 2009/10/30
Y1 - 2009/10/30
N2 - 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.
AB - 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.
KW - DNA
KW - SYSBIO
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U2 - 10.1016/j.cell.2009.08.037
DO - 10.1016/j.cell.2009.08.037
M3 - Article
C2 - 19879846
AN - SCOPUS:70350340058
VL - 139
SP - 610
EP - 622
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -