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Genome-Wide Mapping of in Vivo Protein-DNA Interactions
David S. Johnson,1*Ali Mortazavi,2*Richard M. Myers,1Barbara Wold2,3
In vivo protein-DNA interactions connect each transcriptionfactor with its direct targets to form a gene network scaffold.To map these protein-DNA interactions comprehensively acrossentire mammalian genomes, we developed a large-scale chromatinimmunoprecipitation assay (ChIPSeq) based on direct ultrahigh-throughputDNA sequencing. This sequence census method was then used tomap in vivo binding of the neuron-restrictive silencer factor(NRSF; also known as REST, for repressor element–1 silencingtranscription factor) to 1946 locations in the human genome.The data display sharp resolution of binding position [±50base pairs (bp)], which facilitated our finding motifs and allowedus to identify noncanonical NRSF-binding motifs. These ChIPSeqdata also have high sensitivity and specificity [ROC (receiveroperator characteristic) area 0.96] and statistical confidence(P <10–4), properties that were important for inferringnew candidate interactions. These include key transcriptionfactors in the gene network that regulates pancreatic isletcell development.
1 Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305–5120, USA. 2 Biology Division, California Institute of Technology, Pasadena, CA 91125, USA. 3 California Institute of Technology Beckman Institute, Pasadena, CA 91125, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: woldb{at}its.caltech.edu (B.W.); myers{at}shgc.stanford.edu (R.M.M.)
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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. 
To whom correspondence should be addressed. E-mail: 
