Combinatorial bZIP dimers define complex DNA-binding specificity landscapes

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Data availability
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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

The following data sets were generated

(2017) Data from: Combinatorial dimerization of human bZIP factors confers preferences for different classes of DNA binding sites
Publicly available on the Ansari Lab (https://ansarilab.biochem.wisc.edu/).

https://ansarilab.biochem.wisc.edu/computation.html

The following previously published data sets were used

(2013) Functional Identification of Critical Bmi1 target genes in Neural Progenitor and Malignant Glioma cells
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE33912).

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33912
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5. Nitta KR
6. Rastas P
7. Morgunova E
8. Enge M
9. Taipale M
10. Wei G
11. Palin K
12. Vaquerizas JM
13. Vincentelli R
14. Luscombe NM
15. Hughes TR
16. Lemaire P
17. Ukkonen E
18. Kivioja T
19. Taipale J
(2017) DNA-binding specificities of human transcription factors
Publicly available at the EMBL European Nucleotide Archive (accession no: PRJEB3289).

http://www.ebi.ac.uk/ena/data/view/PRJEB3289

Article and author information

Author details

Jose A Rodriguez-Martinez

Department of Biochemistry, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1191-2887
Aaron W Reinke

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7612-5342
Devesh Bhimsaria

Department of Biochemistry, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Amy E Keating

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Aseem Z Ansari

Department of Biochemistry, University of Wisconsin-Madison, Madison, United States

For correspondence
azansari@wisc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1432-4498

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

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.