Genome-Wide Mapping of in Vivo Protein-DNA Interactions

by: David S Johnson, Ali Mortazavi, Richard M Myers, Barbara Wold

Science (31 May 2007), 1141319.

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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 ultra-high-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. 10.1126/science.1141319

@article{citeulike:1362387, 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 ultra-high-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. 10.1126/science.1141319}, author = {Johnson, David S. and Mortazavi, Ali and Myers, Richard M. and Wold, Barbara }, citeulike-article-id = {1362387}, doi = {http://dx.doi.org/10.1126/science.1141319}, journal = {Science}, keywords = {biotech, chipseq, dna-protein\_interaction, sequencing}, month = {May}, pages = {1141319+}, posted-at = {2007-06-13 20:17:23}, priority = {2}, title = {Genome-Wide Mapping of in Vivo Protein-DNA Interactions}, url = {http://dx.doi.org/10.1126/science.1141319}, year = {2007} }

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TY - JOUR ID - citeulike:1362387 L3 - citeulike-article-id:1362387 N2 - 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 ultra-high-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. 10.1126/science.1141319 JF - Science TI - Genome-Wide Mapping of in Vivo Protein-DNA Interactions SP - 1141319 KW - biotech KW - chipseq KW - dna-protein_interaction KW - sequencing AU - Johnson, David AU - Mortazavi, Ali AU - Myers, Richard AU - Wold, Barbara PY - 2007/05/31/ UR - http://dx.doi.org/10.1126/science.1141319 ER -

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