Yella, VR and Bhimsaria, D and Ghoshdastidar, D and RodrÃguez-MartÃnez, JA and Ansari, AZ and Bansal, M (2018) Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif. In: Nucleic Acids Research, 46 (22). pp. 11883-11897.
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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.
| Item Type: | Journal Article |
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| Publication: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | basic leucine zipper transcription factor; homeodomain protein; transcription factor; zinc finger protein; basic leucine zipper transcription factor; DNA; homeodomain protein; protein binding; zinc finger protein, Article; binding affinity; computer model; conformation; controlled study; correlation analysis; DNA binding; DNA duplex stability; DNA flanking region; DNA flexibility; DNA sequence; DNA structure; high throughput screening; in vitro study; molecular recognition; nonhuman; phenotypic plasticity; priority journal; protein motif; alpha helix; animal; beta sheet; binding site; cell free system; chemistry; genetic transcription; genetics; human; metabolism; nucleotide motif; nucleotide sequence; protein domain, Animals; Base Sequence; Basic-Leucine Zipper Transcription Factors; Binding Sites; Cell-Free System; DNA; Homeodomain Proteins; 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 |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 03 Aug 2022 11:02 |
| Last Modified: | 03 Aug 2022 11:02 |
| URI: | https://eprints.iisc.ac.in/id/eprint/75266 |
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