High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells

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.

The following footprint files are in BED format with the first three columns indicating the genomic position (chromosome, start, end) and the last containing significant motif matches for transcription factors determined using the STAMP program. Footprints were calculated using the hg18 assembly. Footprints for hg19 were created by lifting hg18 footprints, and positions may not be as accurate: