SMiLE-seq identifies binding motifs of single and dimeric transcription factors - PubMed

Affiliations

• PMID: 28092692
• DOI: 10.1038/nmeth.4143

SMiLE-seq identifies binding motifs of single and dimeric transcription factors

Alina Isakova et al. Nat Methods. 2017 Mar.

Abstract

Resolving the DNA-binding specificities of transcription factors (TFs) is of critical value for understanding gene regulation. Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays. De novo motif discovery on all JUN-FOS heterodimers and several nuclear receptor-TF complexes provided novel insights into partner-specific heterodimer DNA-binding preferences. We also successfully analyzed the DNA-binding properties of uncharacterized human C2H2 zinc-finger proteins and validated several using ChIP-exo.

Comment in

• Technique: SMiLE-seq illuminates transcription factor motifs.

  Starling S. Starling S. Nat Rev Genet. 2017 Mar;18(3):144-145. doi: 10.1038/nrg.2017.5. Epub 2017 Jan 31. Nat Rev Genet. 2017. PMID: 28138146 No abstract available.

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