期刊
NATURE METHODS
卷 5, 期 9, 页码 829-834出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.1246
关键词
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资金
- US National Institutes of Health [5 U01 HG003162, 1 U54-HG004576]
- Stanford Pathology and Genetics Ultra-High Throughput Sequencing Initiative
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG003162, U54HG004576] Funding Source: NIH RePORTER
Molecular interactions between protein complexes and DNA mediate essential gene-regulatory functions. Uncovering such interactions by chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) has recently become the focus of intense interest. We here introduce quantitative enrichment of sequence tags (QuEST), a powerful statistical framework based on the kernel density estimation approach, which uses ChIP-Seq data to determine positions where protein complexes contact DNA. Using QuEST, we discovered several thousand binding sites for the human transcription factors SRF, GABP and NRSF at an average resolution of about 20 base pairs. MEME motif-discovery tool-based analyses of the QuEST-identified sequences revealed DNA binding by cofactors of SRF, providing evidence that cofactor binding specificity can be obtained from ChIP-Seq data. By combining QuEST analyses with Gene Ontology (GO) annotations and expression data, we illustrate how general functions of transcription factors can be inferred.
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