Combinatorial bZIP dimers display complex DNA-binding specificity landscapes

• DOI: 10.7554/elife.19272
• Publication Date: 2017-02-10T13:00:14Z
• Authors: José A Rodríguez-...; Aaron W Reinke; Devesh Bhimsaria; Amy E Keating; Aseem Z Ansari
• Keywords: bZIP domain

How transcription factor dimerization impacts DNA-binding specificity is poorly understood. Guided by protein properties, we examined DNA binding specificities of 270 human bZIP pairs. interactomes 80 heterodimers and 22 homodimers revealed that 72% heterodimer motifs correspond to conjoined half-sites preferred partnering monomers. Remarkably, the remaining are composed variably-spaced (12%) or ‘emergent’ sites (16%) cannot be readily inferred from half-site preferences These were biochemically validated EMSA-FRET analysis in vivo ChIP-seq data cell lines. Focusing on ATF3, observed distinct cognate site conferred different partners, demonstrated genome-wide ATF3 best explained considering many dimers which it participates. Importantly, our compendium bZIP-DNA predicted 156 disease associated SNPs, only 20 previously annotated with known motifs.