Genome-Wide Aryl Hydrocarbon Receptor-DNA Binding Reveal Tissue-Specific Binding Determinants
- Description
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ligand-activated AhR binds to DNA at dioxin response elements (DREs). Most DREs in accessible chromatin are not bound by TCDD-activated AhR, and DREs accessible in multiple tissues can be bound in some and unbound in others. This study developed interpretable machine learning models predicting the AhR binding status of DREs in MCF-7, GM17212, and HepG2 cells, as well as primary hepatocytes. The dataset includes ChIP sequencing data, which indicate that AhR binding is driven by a complex interaction of tissue-agnostic DRE flanking DNA sequence and tissue-specific local chromatin context.
Access
- Restrictions
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Free to All
- Instructions
- ChIP sequencing of primary hepatocytes generated in this study has been deposited to Gene Expression Omnibus (GEO). All other datasets used for the creation of input features are available on GEO and ENCODE. The code used to download, prepare, and preprocess the data, as well as to create, optimize, and evaluate the machine learning models is available at GitHub.
- Grant Support
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Institute for Cyber-Enabled Research/Michigan State UniversityAgBioResearch/Michigan State UniversityNational Institute of Food and Agriculture/United States Department of Agriculture