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Genome-wide mapping of in vivo protein-DNA interactions
Author(s): Johnson DS (Johnson, David S.), Mortazavi A (Mortazavi, Ali), Myers RM (Myers, Richard M.), Wold B (Wold, Barbara)
Source: SCIENCE    Volume: 316    Issue: 5830    Pages: 1497-1502    Published: JUN 8 2007  
Times Cited: 229     References: 7     
Abstract: In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay ( ChIPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor ( NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [ +/- 50 base pairs ( bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also have high sensitivity and specificity [ ROC ( receiver operator characteristic) area >= 0.96] and statistical confidence ( P < 10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development.
Document Type: Article
Language: English
Reprint Address: Wold, B (reprint author), Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
Addresses:
1. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
2. CALTECH, Div Biol, Pasadena, CA 91125 USA
3. CALTECH, Beckman Inst, Pasadena, CA 91125 USA
Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
Subject Category: Multidisciplinary Sciences
IDS Number: 176EE
ISSN: 0036-8075
DOI: 10.1126/science.1141319
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