Presentation 転写因子のアクティビィティは結合サイト及びその周辺領域のDNA特性の関係できまる

河野, 秀俊

Transcription factors (TFs) recognize small DNA sequence motifs directly or through their sequence-dependent structure. While sequence composition and degeneracy are verified to be the defining factors of TF binding specificity, the role of conformational dynamics of the DNA remains poorly understood. With growing evidence from next generation sequencing (NGS) data suggesting the inadequacy of sequence-only models, alternative models for describing the TF binding preferences are required, wherein the conformational dynamics presents an attractive option.Here, we report a novel method (DynaSeq) which accurately predicts DNA-conformational ensembles for genomic targets of TFs. Using DynaSeq, we demonstrate how the dynamics of binding sites and their distal flanking regions can be used to elucidate TF-binding patterns for two model systems: cell type-specific binding of STAT3 and chromatin structural specificity of functional TF classes viz. pioneers, settlers and migrants. We find that TF preferences in both these systems can be accurately explained by the conformational dynamics of their binding sites and their distal flanking DNA regions.

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