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Genome-Wide Mapping of in Vivo Protein-DNA Interactions

Johnson, David S. and Mortazavi, Ali and Myers, Richard M. and Wold, Barbara (2007) Genome-Wide Mapping of in Vivo Protein-DNA Interactions. Science, 316 (5830). pp. 1497-1502. ISSN 0036-8075. doi:10.1126/science.1141319.

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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.

Item Type:Article
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URLURL TypeDescription Information
Mortazavi, Ali0000-0002-4259-6362
Wold, Barbara0000-0003-3235-8130
Additional Information:© 2007 American Association for the Advancement of Science. Received 14 February 2007; accepted 26 April 2007; Published online 31 May 2007. We thank G. Schroth and his group at Solexa/Illumina, Inc., for access to the sequencing platform, without which this work would not have been possible. We thank B. Anton, L. Nguyen, C. Medina, and L. Tsavaler for outstanding experimental work and K. F. McCue for invaluable counsel on statistical analyses. We are grateful to D. Anderson of Caltech for the gift of monoclonal antibody against NRSF. This work was supported by NIH grant U01 HG003162 to R.M.M. with a supplement to B.W. and by a grant from the Caltech Beckman Institute. A.M. was supported by NIH/National Research Service Award 5T32GM07616; B.W. by a Bren Chair endowment at Caltech, and R.M.M. by the Stanford W. Ascherman Chair endowment at Stanford University.
Funding AgencyGrant Number
NIHU01 HG003162
Caltech Beckman InstituteUNSPECIFIED
NIH/National Research Service Award (NRSA)5T32GM07616
Caltech Bren Chair endowmentUNSPECIFIED
Stanford UniversityUNSPECIFIED
Issue or Number:5830
Record Number:CaltechAUTHORS:20141119-082130132
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51935
Deposited By: Tony Diaz
Deposited On:19 Nov 2014 17:15
Last Modified:10 Nov 2021 19:18

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