Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity
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Abstract
Transcription factor (TF) DNA sequence preferences direct their regulatory activity, but are currently known for only ∼1% of eukaryotic TFs. Broadly sampling DNA-binding domain (DBD) types from multiple eukaryotic clades, we determined DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes. We find that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ∼34% of the ∼170,000 known or predicted eukaryotic TFs. Sequences matching both measured and inferred motifs are enriched in chromatin immunoprecipitation sequencing (ChIP-seq) peaks and upstream of transcription start sites in diverse eukaryotic lineages. SNPs defining expression quantitative trait loci in Arabidopsis promoters are also enriched for predicted TF binding sites. Importantly, our motif "library" can be used to identify specific TFs whose binding may be altered by human disease risk alleles. These data present a powerful resource for mapping transcriptional networks across eukaryotes.
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The record
- Venue
- Cell
- Topic
- RNA and protein synthesis mechanisms
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of Toronto
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of General Medical SciencesCanadian Institutes of Health ResearchHoward Hughes Medical Institute
- Keywords
- BiologyInferenceComputational biologyGeneticsTranscription factorSequence (biology)Transcription (linguistics)Evolutionary biologyGeneArtificial intelligence
- Has abstract in OpenAlex
- yes