Cell
Volume 158, Issue 6, 11 September 2014, Pages 1431-1443
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Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

https://doi.org/10.1016/j.cell.2014.08.009Get rights and content
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Highlights

  • DNA binding motifs are known for <2% of eukaryotic transcription factors (TFs)

  • Assaying >1,000 diverse TFs yielded rules for transferring motifs between TFs

  • The resulting “motif library” covers ∼34% of eukaryotic TFs across all major clades

  • The library can be used to understand human and plant SNP mechanisms

Summary

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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