Genome-Wide Mapping of in Vivo Protein-DNA Interactions
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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This locus is within 100 kb of REST, a master negative regulator of neurogenesis.
“this locus is within 100kb of REST, a master negative regulator of neurogenesis163.”
From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [163]
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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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