The orchestrated binding of transcriptional activators and repressors to specific DNA sequences in the context of chromatin defines the regulatory program of eukaryotic genomes. We developed a digital approach to assay regulatory protein occupancy on genomic DNA in vivo by dense mapping of individual DNase I cleavages from intact nuclei using massively parallel DNA sequencing. Analysis of >23 million cleavages across the Saccharomyces cerevisiae genome revealed thousands of protected regulatory protein footprints, enabling de novo derivation of factor binding motifs as well as the identification of hundreds of novel binding sites for major regulators. We observed striking correspondence between nucleotide-level DNase I cleavage patterns and protein-DNA @@ -77,17 +73,15 @@ S. Kuehn, William S. Noble (william-noble@u.washington.edu), Stanley Fields (fields@u.washington.edu) and John A. Stamatoyannopoulos (jstam@stamlab.org).
Hesselberth JR, Chen X, Zhang Z, Sabo PJ, Sandstrom R, Reynolds AP, Thurman RE, Neph S, Kuehn MS, Noble WS et al. Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat Methods. 2009 Apr;6(4):283-9. PMID: 19305407; PMC: PMC2668528
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