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      Enhanced Maps of Transcription Factor Binding Sites Improve Regulatory Networks Learned from Accessible Chromatin Data.

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          Abstract

          Determining where transcription factors (TFs) bind in genomes provides insight into which transcriptional programs are active across organs, tissue types, and environmental conditions. Recent advances in high-throughput profiling of regulatory DNA have yielded large amounts of information about chromatin accessibility. Interpreting the functional significance of these data sets requires knowledge of which regulators are likely to bind these regions. This can be achieved by using information about TF-binding preferences, or motifs, to identify TF-binding events that are likely to be functional. Although different approaches exist to map motifs to DNA sequences, a systematic evaluation of these tools in plants is missing. Here, we compare four motif-mapping tools widely used in the Arabidopsis (Arabidopsis thaliana) research community and evaluate their performance using chromatin immunoprecipitation data sets for 40 TFs. Downstream gene regulatory network (GRN) reconstruction was found to be sensitive to the motif mapper used. We further show that the low recall of Find Individual Motif Occurrences, one of the most frequently used motif-mapping tools, can be overcome by using an Ensemble approach, which combines results from different mapping tools. Several examples are provided demonstrating how the Ensemble approach extends our view on transcriptional control for TFs active in different biological processes. Finally, a protocol is presented to effectively derive more complete cell type-specific GRNs through the integrative analysis of open chromatin regions, known binding site information, and expression data sets. This approach will pave the way to increase our understanding of GRNs in different cellular conditions.

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          Author and article information

          Journal
          Plant Physiol.
          Plant physiology
          American Society of Plant Biologists (ASPB)
          1532-2548
          0032-0889
          October 2019
          : 181
          : 2
          Affiliations
          [1 ] Ghent University, Department of Plant Biotechnology and Bioinformatics, 9052 Ghent, Belgium.
          [2 ] VIB Center for Plant Systems Biology, 9052 Ghent, Belgium.
          [3 ] Bioinformatics Institute Ghent, Ghent University, 9052 Ghent, Belgium.
          [4 ] Ghent University, Department of Plant Biotechnology and Bioinformatics, 9052 Ghent, Belgium klaas.vandepoele@psb.vib-ugent.be.
          Article
          pp.19.00605
          10.1104/pp.19.00605
          6776849
          31345953

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