Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing
Abstract
We developed a method, ChIP-sequencing (ChIP-seq), combining chromatin immunoprecipitation (ChIP) and massively parallel sequencing to identify mammalian DNA sequences bound by transcription factors in vivo. We used ChIP-seq to map STAT1 targets in interferon-gamma (IFN-gamma)-stimulated and unstimulated human HeLa S3 cells, and compared the method's performance to ChIP-PCR and to ChIP-chip for four chromosomes. By ChIP-seq, using 15.1 and 12.9 million uniquely mapped sequence reads, and an estimated false discovery rate of less than 0.001, we identified 41,582 and 11,004 putative STAT1-binding regions in stimulated and unstimulated cells, respectively. Of the 34 loci known to contain STAT1 interferon-responsive binding sites, ChIP-seq found 24 (71%). ChIP-seq targets were enriched in sequences similar to known STAT1 binding motifs. Comparisons with two ChIP-PCR data sets suggested that ChIP-seq sensitivity was between 70% and 92% and specificity was at least 95%.
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DNA from triplicate pooled ChIP experiments was purified and sequenced.
“DNA from triplicate pooled ChIP experiments was purified by 8% PAGE to obtain 100-300-bp fragments and sequenced on an Illumina 1G sequencer as previously reported (Robertson et al. 2007).”
From Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver (2010) · cites this paper as Robertson et al. 2007
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- Authors
- Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., Thiessen, N., Griffith, O. L., He, A., Marra, M., Snyder, M., & Jones, S.
- Affiliations
- BC Cancer Agency (CA)
- Yale University (US)
- Corresponding author
- Jones, Steven
- ORCID
- Venue
- Nature Methods
- Published
- 2007-06-11
- Volume
- 4
- Issue
- 8
- Pages
- 651-657
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2059699217
- Cited by
- 1,454
- References
- 5
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 51 · 2023: 57 · 2022: 55 · 2021: 45 · 2020: 51 · 2019: 42 · 2018: 59 · 2017: 51 · 2016: 58 · 2015: 73 · 2014: 84 · 2013: 94 · 2012: 124
- FWCI
- 52.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada's Michael Smith Genome Sciences Centre
- Genome British Columbia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- ChIP-seq, STAT1, transcription factor binding sites, interferon-gamma signaling, HeLa S3 cells, genome-wide binding site mapping, false discovery rate, method sensitivity and specificity
- MeSH terms
- DNA, Protein Binding, Polymerase Chain Reaction, Genome, Chromatin Immunoprecipitation, STAT1 Transcription Factor
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