TY - JOUR A1 - Boyle, Alan P. A1 - Song, Lingyun A1 - Lee, Bum-Kyu A1 - London, Darin A1 - Keefe, Damian A1 - Birney, Ewan A1 - Iyer, Vishwanath R. A1 - Crawford, Gregory E. A1 - Furey, Terrence S. T1 - High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells Y1 - 2011/03/01 JF - Genome Research JO - Genome Research SP - 456 EP - 464 DO - 10.1101/gr.112656.110 VL - 21 IS - 3 UR - http://genome.cshlp.org/content/21/3/456.abstract N2 - Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds of thousands of base-pair resolution in vivo footprints in human cells that precisely mark individual transcription factor–DNA interactions. These annotations provide a unique resource for the investigation of cis-regulatory elements. We find that footprints for specific transcription factors correlate with ChIP-seq enrichment and can accurately identify functional versus nonfunctional transcription factor motifs. We also find that footprints reveal a unique evolutionary conservation pattern that differentiates functional footprinted bases from surrounding DNA. Finally, detailed analysis of CTCF footprints suggests multiple modes of binding and a novel DNA binding motif upstream of the primary binding site. ER -