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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.

SUBMITTER: Boyle AP 

PROVIDER: S-EPMC3044859 | biostudies-other | 2011 Mar

REPOSITORIES: biostudies-other

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

Boyle Alan P AP   Song Lingyun L   Lee Bum-Kyu BK   London Darin D   Keefe Damian D   Birney Ewan E   Iyer Vishwanath R VR   Crawford Gregory E GE   Furey Terrence S TS  

Genome research 20101124 3


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 t  ...[more]

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