Combinatorial bZIP dimers define complex DNA-binding specificity landscapes
- University of Wisconsin-Madison, United States
- Massachusetts Institute of Technology, United States
Abstract
How transcription factor dimerization impacts DNA binding specificity is poorly understood. Guided by protein dimerization properties, we examined DNA binding specificities of 270 human bZIP pairs. DNA interactomes of 80 heterodimers and 22 homodimers revealed that 72% of heterodimer motifs correspond to conjoined half-sites preferred by partnering monomers. Remarkably, the remaining motifs are composed of variably-spaced half-sites (12%) or 'emergent' sites (16%) that cannot be readily inferred from half-site preferences of partnering monomers. These binding sites were biochemically validated by EMSA-FRET analysis and validated in vivo by ChIP-seq data from human cell lines. Focusing on ATF3, we observed distinct cognate site preferences conferred by different bZIP partners, and demonstrated that genome-wide binding of ATF3 is best explained by considering many dimers in which it participates. Importantly, our compendium of bZIP-DNA interactomes predicted bZIP binding to 156 disease associated SNPs, of which only 20 were previously annotated with known bZIP motifs.
Data availability
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Data from: Combinatorial dimerization of human bZIP factors confers preferences for different classes of DNA binding sitesPublicly available on the Ansari Lab (https://ansarilab.biochem.wisc.edu/).
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Functional Identification of Critical Bmi1 target genes in Neural Progenitor and Malignant Glioma cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE33912).
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DNA-binding specificities of human transcription factorsPublicly available at the EMBL European Nucleotide Archive (accession no: PRJEB3289).
Article and author information
Author details
Jose A Rodriguez-Martinez
Funding
National Institutes of Health (R01GM096466)
- Amy E Keating
W. M. Keck Foundation
- Aseem Z Ansari
National Institutes of Health (U01HL099773)
- Aseem Z Ansari
National Institutes of Health (R01CA133508)
- Aseem Z Ansari
National Institutes of Health (T32HG002760)
- Jose A Rodriguez-Martinez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Rodriguez-Martinez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Combinatorial bZIP dimers define complex DNA-binding specificity landscapes
eLife 6:e19272.
https://doi.org/10.7554/eLife.19272
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