Transcription factor (TF) recognition is dictated by the underlying DNA motif sequence specific for each TF. Here, we reveal that DNA sequence repeat symmetry plays a central role in defining TF-DNA-binding preferences. In particular, we find that different TFs bind similar symmetry patterns in the context of different developmental layers. Most TFs possess dominant preferences for similar DNA repeat symmetry types. However, in some cases, preferences of specific TFs are changed during differentiation, suggesting the importance of information encoded outside of known motif regions. Histone modifications also exhibit strong preferences for similar DNA repeat symmetry patterns unique to each type of modification. Next, using an in vivo reporter assay, we show that gene expression in embryonic stem cells can be positively modulated by the presence of genomic and computationally designed DNA oligonucleotides containing identified nonconsensus-repetitive sequence elements. This supports the hypothesis that certain nonconsensus-repetitive patterns possess a functional ability to regulate gene expression. We also performed a solution NMR experiment to probe the stability of double-stranded DNA via imino proton resonances for several double-stranded DNA sequences characterized by different repetitive patterns. We suggest that such local stability might play a key role in determining TF-DNA binding preferences. Overall, our findings show that despite the enormous sequence complexity of the TF-DNA binding landscape in differentiating embryonic stem cells, this landscape can be quantitatively characterized in simple terms using the notion of DNA sequence repeat symmetry.

中文翻译：

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胚胎干细胞中的转录因子结合受 DNA 序列重复对称性的限制

转录因子 (TF) 识别由特定于每个 TF 的潜在 DNA 基序序列决定。在这里，我们揭示了 DNA 序列重复对称性在定义 TF-DNA 结合偏好方面起着核心作用。特别是，我们发现不同的 TF 在不同发育层的背景下结合了相似的对称模式。大多数 TF 对相似的 DNA 重复对称类型具有显性偏好。然而，在某些情况下，特定 TF 的偏好在分化过程中会发生变化，这表明在已知基序区域之外编码的信息的重要性。组蛋白修饰还表现出对每种修饰类型独有的类似 DNA 重复对称模式的强烈偏好。接下来，使用体内报告基因检测，我们表明胚胎干细胞中的基因表达可以通过基因组和计算设计的 DNA 寡核苷酸的存在来积极调节，这些寡核苷酸包含已识别的非一致重复序列元素。这支持了某些非共识重复模式具有调节基因表达的功能能力的假设。我们还进行了溶液核磁共振实验，以通过亚氨基质子共振探测双链 DNA 的稳定性，这些双链 DNA 具有不同的重复模式特征。我们建议这种局部稳定性可能在确定 TF-DNA 结合偏好方面发挥关键作用。总体而言，我们的研究结果表明，尽管胚胎干细胞分化过程中 TF-DNA 结合具有巨大的序列复杂性，