Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif.
Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif.
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DOI：
10.1093/nar/gky1057
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发表时间：
2018-12-14
影响因子：
14.9
通讯作者：
Bansal M
中科院分区：
文献类型：
--
作者：
Yella VR;Bhimsaria D;Ghoshdastidar D;Rodríguez-Martínez JA;Ansari AZ;Bansal M
基因的空间和时间表达对于维持表型完整性至关重要。转录因子（TF）通过与基因组中的特定DNA序列结合来调节表达模式。沿着核心结合基序，侧翼序列环境可以在DNA-TF识别中发挥作用。在这里，我们采用高通量的体外和计算机分析，以了解侧翼序列的同源位点结合的三个最普遍的真核TF家族（锌指，同源结构域和bZIP）的影响。每个TF对整个DNA序列空间的体外结合偏好与广泛的DNA结构参数（包括DNA柔性）相关。结果表明，侧翼区的构象可塑性调节某些TF家族的结合亲和力。DNA双链体稳定性和小沟宽度在DNA-TF识别中也起重要作用，但在每种特定情况下它们如何确切地影响结合方面有所不同。我们的分析进一步揭示，优选的侧翼序列的结构特征是不通用的，因为类似的DNA结合折叠可以采用不同的DNA识别模式。
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.
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影响因子：
46.9
作者：
Berger, Michael F.;Philippakis, Anthony A.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
影响因子：
7
作者：
Dror I;Golan T;Levy C;Rohs R;Mandel-Gutfreund Y
通讯作者：
Mandel-Gutfreund Y
影响因子：
5.6
作者：
GORIN, AA;ZHURKIN, VB;OLSON, WK
通讯作者：
OLSON, WK
影响因子：
8.8
作者：
Chen Y;Bates DL;Dey R;Chen PH;Machado AC;Laird-Offringa IA;Rohs R;Chen L
通讯作者：
Chen L
DOI：
10.1073/pnas.1811431115
发表时间：
2018-11-06
影响因子：
11.1
作者：
Bhimsaria, Devesh;Rodriguez-Martinez, Jose A.;Ansari, Aseem Z.
通讯作者：
Ansari, Aseem Z.