Publications [#363315] of Alexander J. Hartemink
search PubMed.Journal articles or Book chapters PUBLISHED
- Luo, K; Zhong, J; Safi, A; Hong, LK; Tewari, AK; Song, L; Reddy, TE; Ma, L; Crawford, GE; Hartemink, AJ, Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data.,
Genome Res, vol. 32 no. 6
(June, 2022),
pp. 1183-1198 [doi] .
(last updated on 2024/07/22)Abstract:
Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the TF occupancy landscape, let alone quantify how it changes across conditions. We developed TF occupancy profiler (TOP), a Bayesian hierarchical regression framework, to profile genome-wide quantitative occupancy of numerous TFs using data from a single chromatin accessibility experiment (DNase- or ATAC-seq). TOP is supervised, and its hierarchical structure allows it to predict the occupancy of any sequence-specific TF, even those never assayed with ChIP. We used TOP to profile the quantitative occupancy of hundreds of sequence-specific TFs at sites throughout the genome and examined how their occupancies changed in multiple contexts: in approximately 200 human cell types, through 12 h of exposure to different hormones, and across the genetic backgrounds of 70 individuals. TOP enables cost-effective exploration of quantitative changes in the landscape of TF binding.