High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells
- Alan P. Boyle1,
- Lingyun Song1,2,
- Bum-Kyu Lee3,
- Darin London1,
- Damian Keefe4,
- Ewan Birney4,
- Vishwanath R. Iyer3,
- Gregory E. Crawford1,2,5 and
- Terrence S. Furey1,5
- 1 Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA;
- 2 Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina 27708, USA;
- 3 Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712, USA;
- 4 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1RQ, United Kingdom
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.
Footnotes
-
↵5 Corresponding authors.
E-mail terry.furey{at}duke.edu.
E-mail greg.crawford{at}duke.edu.
-
[Supplemental material is available for this article. The sequence data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession nos. GSE19622 and GSE25442.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.112656.110.
- Received July 8, 2010.
- Accepted November 1, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.
