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

Shaohui Hu; Zhi Xie; Akishi Onishi; Xueping Yu; Lizhi Jiang; Jimmy Lin; Hee sool Rho; Crystal Woodard; Hong Wang; Jun Seop Jeong; Shunyou Long; Xiaofei He; Herschel Wade; Seth Blackshaw; Jiang Qian; Heng Zhu

doi:10.1016/j.cell.2009.08.037

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

Shaohui Hu, Zhi Xie, Akishi Onishi, Xueping Yu, Lizhi Jiang, Jimmy Lin, Hee sool Rho, Crystal Woodard, Hong Wang, Jun Seop Jeong, Shunyou Long, Xiaofei He, Herschel Wade, Seth Blackshaw, Jiang Qian, Heng Zhu

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	610-622
Number of pages	13
Journal	Cell
Volume	139
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2009.08.037
State	Published - Oct 30 2009

Keywords

DNA
SYSBIO

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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

In: Cell, Vol. 139, No. 3, 30.10.2009, p. 610-622.

Research output: Contribution to journal › Article › peer-review

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. / Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling. In: Cell. 2009 ; Vol. 139, No. 3. pp. 610-622.

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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.",

keywords = "DNA, SYSBIO",

author = "Shaohui Hu and Zhi Xie and Akishi Onishi and Xueping Yu and Lizhi Jiang and Jimmy Lin and Rho, {Hee sool} and Crystal Woodard and Hong Wang and Jeong, {Jun Seop} and Shunyou Long and Xiaofei He and Herschel Wade and Seth Blackshaw and Jiang Qian and Heng Zhu",

note = "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. ",

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doi = "10.1016/j.cell.2009.08.037",

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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

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

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