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Genome Res. 2011 Mar;21(3):456-64. doi: 10.1101/gr.112656.110. Epub 2010 Nov 24.

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

Author information

1
Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.

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.

PMID:
21106903
PMCID:
PMC3044859
DOI:
10.1101/gr.112656.110
[Indexed for MEDLINE]
Free PMC Article

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