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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)610-622
Number of pages13
JournalCell
Volume139
Issue number3
DOIs
StatePublished - Oct 30 2009

Keywords

  • DNA
  • SYSBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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