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

Abstract

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.

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Affiliated Institutions

• European Bioinformatics Institute GB
• Wellcome Trust GB
• Duke Medical Center US
• Duke University US
• The University of Texas at Austin US

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