Cited by 2,927Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

Genome-Wide Mapping of in Vivo Protein-DNA Interactions

Johnson, David S., Mortazavi, Ali, Myers, Richard M., Wold, Barbara·2007·Science

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.

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Crossref · 10.1126/science.1141319

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Authors
Johnson, D. S., Mortazavi, A., Myers, R. M., & Wold, B.
Affiliations
California Institute of Technology (US)
Corresponding author
  • Johnson, David S.
  • Mortazavi, Ali
  • Myers, Richard M.
  • Wold, Barbara
Venue
Science
Published
2007-06-08
Volume
316
Issue
5830
Pages
1497-1502
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2129795133
Cited by
2,927
References
23
Citations by year
2026: 97 · 2025: 131 · 2024: 124 · 2023: 142 · 2022: 134 · 2021: 144 · 2020: 144 · 2019: 133 · 2018: 141 · 2017: 110 · 2016: 132 · 2015: 178 · 2014: 172 · 2013: 169 · 2012: 192
FWCI
72.51
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • National Human Genome Research Institute (U01HG003162)
  • National Institute of General Medical Sciences (T32GM007616)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
protein-DNA interactions, transcription factor binding sites, rest, NRSF, ChIP-seq, gene regulatory networks, pancreatic islet development, transcriptional repression
MeSH terms
RE1-Silencing Transcription Factor, Algorithms, Binding Sites, DNA, DNA-Binding Proteins, Humans, Synaptic Transmission, Neurons, Promoter Regions, Genetic, Protein Binding, Repressor Proteins, Sensitivity and Specificity, T-Lymphocytes, Transcription Factors, Transcription, Genetic, Genome, Human, Zinc Fingers, Sequence Analysis, DNA, Amino Acid Motifs, MicroRNAs, Chromatin Immunoprecipitation, Insulin-Secreting Cells, Gene Regulatory Networks

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