ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation

Mette Bentsen, Philipp Goymann, Hendrik Schultheis, Kathrin Klee, Anastasiia Petrova, René Wiegandt, Annika Fust, Jens Preussner, Carsten Kuenne, Thomas Braun, Johnny Kim and Mario Looso ()
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Mette Bentsen: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Philipp Goymann: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Hendrik Schultheis: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Kathrin Klee: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Anastasiia Petrova: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
René Wiegandt: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Annika Fust: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Jens Preussner: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Carsten Kuenne: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research
Thomas Braun: German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main
Johnny Kim: German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main
Mario Looso: Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract While footprinting analysis of ATAC-seq data can theoretically enable investigation of transcription factor (TF) binding, the lack of a computational tool able to conduct different levels of footprinting analysis has so-far hindered the widespread application of this method. Here we present TOBIAS, a comprehensive, accurate, and fast footprinting framework enabling genome-wide investigation of TF binding dynamics for hundreds of TFs simultaneously. We validate TOBIAS using paired ATAC-seq and ChIP-seq data, and find that TOBIAS outperforms existing methods for bias correction and footprinting. As a proof-of-concept, we illustrate how TOBIAS can unveil complex TF dynamics during zygotic genome activation in both humans and mice, and propose how zygotic Dux activates cascades of TFs, binds to repeat elements and induces expression of novel genetic elements.

Date: 2020
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DOI: 10.1038/s41467-020-18035-1

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