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Cited by 73Genomics and Chromatin DynamicsChromatin Remodeling and CancerGenomics and Phylogenetic Studies

Non-targeted transcription factors motifs are a systemic component of ChIP-seq datasets

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Worsley Hunt, Rebecca, Wasserman, Wyeth W·2014·Genome Biology
DOI 10.1186/s13059-014-0412-4PMC PMC4165360
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Abstract

Background: The global effort to annotate the non-coding portion of the human genome relies heavily on chromatin immunoprecipitation data generated with high-throughput DNA sequencing (ChIP-seq). ChIP-seq is generally successful in detailing the segments of the genome bound by the immunoprecipitated transcription factor (TF), however almost all datasets contain genomic regions devoid of the canonical motif for the TF. It remains to be determined if these regions are related to the immunoprecipitated TF or whether, despite the use of controls, there is a portion of peaks that can be attributed to other causes. Results: Analyses across hundreds of ChIP-seq datasets generated for sequence-specific DNA binding TFs reveal a small set of TF binding profiles for which predicted TF binding site motifs are repeatedly observed to be significantly enriched. Grouping related binding profiles, the set includes: CTCF-like, ETS-like, JUN-like, and THAP11 profiles. These frequently enriched profiles are termed ‘zingers’ to highlight their unanticipated enrichment in datasets for which they were not the targeted TF, and their potential impact on the interpretation and analysis of TF ChIP-seq data. Peaks with zinger motifs and lacking the ChIPped TF’s motif are observed to compose up to 45% of a ChIP-seq dataset. There is substantial overlap of zinger motif containing regions between diverse TF datasets, suggesting a mechanism that is not TF-specific for the recovery of these regions. Conclusions: Based on the zinger regions proximity to cohesin-bound segments, a loading station model is proposed. Further study of zingers will advance understanding of gene regulation.

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  • It remains unknown what proportion of candidate enhancers identified solely by biochemical marks are technical false positives or have enhancer-like features but no meaningful impact on expression of cis-encoded genes.

    “Although unquestionably useful, it remains unknown what proportion of candidate enhancers identified solely by biochemical marks are technical false positives130-132 or a product of having enhancer-like biochemical features but no meaningful impact on the expression of cis encoded genes133.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [131]

    The Background (page unavailable) says ChIP-seq peaks can be shaped by technical influences, including non-specific antibody pull-down, and leaves open whether some peaks arise from other causes. That supports the possibility of technical false positives, but the paper examines transcription-factor ChIP-seq peaks, not the proportion of biochemically identified candidate enhancers that are false positives. The separate claim about enhancer-like features having no meaningful effect on cis-gene expression is attached to citation 133, not this source. (LLM, conf=0.83)

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Authors
Worsley Hunt, R., & Wasserman, W. W.
Affiliations
University of British Columbia (CA)
Corresponding author
Wasserman, Wyeth W
ORCID
Wasserman, Wyeth W
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2014-07-29
Volume
15
Issue
7
Pages
412-412
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-014-0412-4
PMC
PMC4165360
OpenAlex
W2146890600
Cited by
73
References
44
Citations by year
2026: 7 · 2025: 3 · 2024: 9 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 11 · 2015: 6
FWCI
3.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • cIRcle (University of British Columbia) (submittedVersion, cc-by)
  • Open Collections
Funders
  • Genome Canada (ABC4DE)
  • Michael Smith Health Research BC
  • National Institutes of Health
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
  • National Institute of General Medical Sciences (R01GM084875)
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, ChIP-seq, sequence-specific DNA binding, gene expression regulation
MeSH terms
Animals, DNA, Humans, Models, Genetic, Transcription Factors, Sequence Analysis, DNA, Computational Biology, Databases, Genetic, Chromatin Immunoprecipitation, Mice, Molecular Sequence Annotation, High-Throughput Nucleotide Sequencing

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