Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data
Open accessAbstract
Accurate functional annotation of regulatory elements is essential for understanding global gene regulation. Here, we report a genome-wide map of 827,000 transcription factor binding sites in human lymphoblastoid cell lines, which is comprised of sites corresponding to 239 position weight matrices of known transcription factor binding motifs, and 49 novel sequence motifs. To generate this map, we developed a probabilistic framework that integrates cell- or tissue-specific experimental data such as histone modifications and DNase I cleavage patterns with genomic information such as gene annotation and evolutionary conservation. Comparison to empirical ChIP-seq data suggests that our method is highly accurate yet has the advantage of targeting many factors in a single assay. We anticipate that this approach will be a valuable tool for genome-wide studies of gene regulation in a wide variety of cell types or tissues under diverse conditions.
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Using DNase hypersensitivity or ATAC-seq data to infer open chromatin, followed by combining transcription factor binding with open chromatin footprinting, can provide a powerful and comprehensive way to identify tissue-specific transcription factor regulation.
“There is compelling evidence that using DNase hypersensitivity or ATAC-seq data to infer open chromatin, followed by combining transcription factor binding with open chromatin footprinting, can provide a powerful and comprehensive way to identify tissue-specific transcription factor regulation60,61.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [61]
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- Authors
- Pique-Regi, R., Degner, J. F., Pai, A. A., Gaffney, D. J., Gilad, Y., & Pritchard, J. K.
- Affiliations
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-11-24
- Volume
- 21
- Issue
- 3
- Pages
- 447-455
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC3044858
- OpenAlex
- W2142410561
- Cited by
- 521
- References
- 43
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 19 · 2021: 43 · 2020: 34 · 2019: 37 · 2018: 53 · 2017: 42 · 2016: 48 · 2015: 51 · 2014: 57 · 2013: 34 · 2012: 42
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genome Research (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust
- National Institutes of Health
- National Human Genome Research Institute
- 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 › Genomics and Phylogenetic Studies
- Keywords
- transcription factor binding sites, chromatin accessibility, DNase I cleavage, histone modifications, position weight matrices, gene expression regulation, lymphoblastoid cell lines, probabilistic inference, evolutionary conservation
- MeSH terms
- Binding Sites, Cells, Cultured, Chromatin, Histones, Humans, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Genome, Sequence Analysis, DNA, Computational Biology, Oligonucleotide Array Sequence Analysis, Chromatin Immunoprecipitation, DNA Cleavage, Position-Specific Scoring Matrices, Molecular Sequence Annotation
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