Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif

Abstract Spatial and temporal expression of genes is essential for maintaining phenotype integrity. Transcription factors (TFs) modulate expression patterns by binding to specific DNA sequences in the genome. Along with the core binding motif, the flanking sequence context can play a role in DNA-TF...

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Bibliographic Details
Published in:Nucleic acids research 2018-12, Vol.46 (22), p.11883-11897
Main Authors: Yella, Venkata Rajesh, Bhimsaria, Devesh, Ghoshdastidar, Debostuti, Rodríguez-Martínez, José A, Ansari, Aseem Z, Bansal, Manju
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Basic-Leucine Zipper Transcription Factors - chemistry
Basic-Leucine Zipper Transcription Factors - genetics
Basic-Leucine Zipper Transcription Factors - metabolism
Binding Sites
Cell-Free System - chemistry
Cell-Free System - metabolism
DNA - chemistry
DNA - genetics
DNA - metabolism
Genomics
Homeodomain Proteins - chemistry
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Nucleic Acid Conformation
Nucleotide Motifs
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Transcription, Genetic
Zinc Fingers - genetics
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Summary:Abstract Spatial and temporal expression of genes is essential for maintaining phenotype integrity. Transcription factors (TFs) modulate expression patterns by binding to specific DNA sequences in the genome. Along with the core binding motif, the flanking sequence context can play a role in DNA-TF recognition. Here, we employ high-throughput in vitro and in silico analyses to understand the influence of sequences flanking the cognate sites in binding of three most prevalent eukaryotic TF families (zinc finger, homeodomain and bZIP). In vitro binding preferences of each TF toward the entire DNA sequence space were correlated with a wide range of DNA structural parameters, including DNA flexibility. Results demonstrate that conformational plasticity of flanking regions modulates binding affinity of certain TF families. DNA duplex stability and minor groove width also play an important role in DNA-TF recognition but differ in how exactly they influence the binding in each specific case. Our analyses further reveal that the structural features of preferred flanking sequences are not universal, as similar DNA-binding folds can employ distinct DNA recognition modes.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky1057