High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells
- Alan P Boyle1,
- Lingyun Song1,
- Bum-Kyu Lee2,
- Darin London1,
- Damian Keefe3,
- Ewan Birney3,
- Vishwanath R Iyer2,
- Gregory E Crawford1 and
- Terrence S Furey1,4
- * Corresponding author; email: terry.furey{at}duke.edu
Abstract
Regulation of gene transcription in diverse cell types is largely determined by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNaseI 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 vs. non-functional 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.
- Received July 8, 2010.
- Accepted November 1, 2010.
- Copyright © 2010, Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
