Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data across 27 Tissue Types

• Published in: Cell reports (Cambridge) Vol. 32; no. 7; p. 108029
• Main Authors: Funk, Cory C., Casella, Alex M., Jung, Segun, Richards, Matthew A., Rodriguez, Alex, Shannon, Paul, Donovan-Maiye, Rory, Heavner, Ben, Chard, Kyle, Xiao, Yukai, Glusman, Gustavo, Ertekin-Taner, Nilufer, Golde, Todd E., Toga, Arthur, Hood, Leroy, Van Horn, John D., Kesselman, Carl, Foster, Ian, Madduri, Ravi, Price, Nathan D., Ament, Seth A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.08.2020; Elsevier
• Subjects: BASIC BIOLOGICAL SCIENCES; Binding Sites - genetics; Deoxyribonucleases - metabolism; DNase-seq; ENCODE; footprinting; gene regulation; Genomics - methods; Humans; motifs; psychiatric genetics; transcription factors; Transcription Factors - metabolism; DNase-seq; psychiatric genetics; footprinting; transcription factors; gene regulation; motifs; ENCODE
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108029

Characterizing the tissue-specific binding sites of transcription factors (TFs) is essential to reconstruct gene regulatory networks and predict functions for non-coding genetic variation. DNase-seq footprinting enables the prediction of genome-wide binding sites for hundreds of TFs simultaneously. Despite the public availability of high-quality DNase-seq data from hundreds of samples, a comprehensive, up-to-date resource for the locations of genomic footprints is lacking. Here, we develop a scalable footprinting workflow using two state-of-the-art algorithms: Wellington and HINT. We apply our workflow to detect footprints in 192 ENCODE DNase-seq experiments and predict the genomic occupancy of 1,515 human TFs in 27 human tissues. We validate that these footprints overlap true-positive TF binding sites from ChIP-seq. We demonstrate that the locations, depth, and tissue specificity of footprints predict effects of genetic variants on gene expression and capture a substantial proportion of genetic risk for complex traits. [Display omitted] •Comprehensive map of TF occupancy in human tissues from DNase-seq footprints•Footprints contain genetic variants associated with changes in gene expression•Tissue-specific associations of footprints with genetic risk for complex traits DNase-seq footprinting provides a means to predict genome-wide binding sites for hundreds of transcription factors (TFs) simultaneously. Funk et al. analyze data from the ENCODE consortium to create a resource of footprints in 27 human tissues, demonstrating associations of tissue-specific TF occupancy with gene regulation and disease risk.