Determination and inference of eukaryotic transcription factor sequence specificity Journal Article
| Authors: | Weirauch, M. T.; Yang, A.; Albu, M.; Cote, A. G.; Montenegro-Montero, A.; Drewe, P.; Najafabadi, H. S.; Lambert, S. A.; Mann, I.; Cook, K.; Zheng, H.; Goity, A.; van Bakel, H.; Lozano, J. C.; Galli, M.; Lewsey, M. G.; Huang, E.; Mukherjee, T.; Chen, X.; Reece-Hoyes, J. S.; Govindarajan, S.; Shaulsky, G.; Walhout, A. J. M.; Bouget, F. Y.; Ratsch, G.; Larrondo, L. F.; Ecker, J. R.; Hughes, T. R. |
| Article Title: | Determination and inference of eukaryotic transcription factor sequence specificity |
| 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. |
| Keywords: | controlled study; promoter region; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; nonhuman; metabolism; allele; protein binding; genetic variability; transcription factor; transcription factors; chromatin immunoprecipitation; promoter regions, genetic; nucleotide sequence; binding site; dna sequence; dna binding; eukaryote; quantitative trait locus; quantitative trait loci; transcription initiation site; sequence analysis, dna; arabidopsis; nucleotide motifs; humans; human; article; nucleotide motif; dna binding domain |
| Journal Title: | Cell |
| Volume: | 158 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2014-09-01 |
| Start Page: | 1431 |
| End Page: | 1443 |
| Language: | English |
| DOI: | 10.1016/j.cell.2014.08.009 |
| PUBMED: | 25215497 |
| PROVIDER: | scopus |
| PMCID: | PMC4163041 |
| DOI/URL: | |
| Notes: | Export Date: 11 February 2015 -- Source: Scopus |
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