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

被引：308

作者：

Hu, Shaohui ^{[2
,4
]}

Xie, Zhi ^{[1
]}

Onishi, Akishi ^{[3
,4
,5
]}

Yu, Xueping ^{[1
]}

Jiang, Lizhi ^{[3
,4
,5
]}

Lin, Jimmy ^{[6
]}

Rho, Hee-sool ^{[2
,4
]}

Woodard, Crystal ^{[2
,4
]}

Wang, Hong ^{[3
,4
,5
]}

Jeong, Jun-Seop ^{[2
,4
]}

Long, Shunyou ^{[4
]}

He, Xiaofei ^{[2
,4
]}

Wade, Herschel ^{[7
]}

Blackshaw, Seth ^{[1
,3
,4
,5
]}

Qian, Jiang ^{[1
,8
]}

Zhu, Heng ^{[2
,4
,8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Ctr High Throughput Biol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Grad Program Cellular & Mol Med, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA

来源：

CELL | 2009年 / 139卷 / 03期

基金：

美国国家卫生研究院;

关键词：

REGULATORY MOTIFS; GENE-EXPRESSION; SYSTEMATIC DISCOVERY; BINDING; MICROARRAY; DATABASE; GENOME; IDENTIFICATION; PREDICTION; SEQUENCES;

D O I：

10.1016/j.cell.2009.08.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：610 / 622

页数：13

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