Data from: Discovery and information-theoretic characterization of transcription factor binding sites that act cooperatively

Transcription factor binding to the surface of DNA regulatory regions is one of the primary causes of regulating gene expression levels. A probabilistic approach to model protein–DNA interactions at the sequence level is through position weight matrices (PWMs) that estimate the joint probability of a DNA binding site sequence by assuming positional independence within the DNA sequence. Here we construct conditional PWMs that depend on the motif signatures in the flanking DNA sequence, by conditioning known binding site loci on the presence or absence of additional binding sites in the flanking sequence of each siteʼs locus. Pooling known sites with similar flanking sequence patterns allows for the estimation of the conditional distribution function over the binding site sequences. We apply our model to the Dorsal transcription factor binding sites active in patterning the Dorsal–Ventral axis of Drosophila development. We find that those binding sites that cooperate with nearby Twist sites on average contain about 0.5 bits of information about the presence of Twist transcription factor binding sites in the flanking sequence. We also find that Dorsal binding site detectors conditioned on flanking sequence information make better predictions about what is a Dorsal site relative to background DNA than detection without information about flanking sequence features.

转录因子（Transcription factor）结合DNA调控区域的表面，是调控基因表达水平的核心机制之一。在序列层面建模蛋白质-DNA相互作用的概率方法，可通过位置权重矩阵（position weight matrices, PWMs）实现——这类矩阵通过假设DNA序列内的位置独立性，估算DNA结合位点序列的联合概率。本文构建了依赖侧翼DNA序列中基序特征的条件式位置权重矩阵：将已知结合位点以每个结合位点侧翼序列中是否存在额外结合位点作为条件进行约束。将具有相似侧翼序列模式的已知结合位点进行合并，即可估算结合位点序列上的条件分布函数。我们将所提模型应用于在果蝇（Drosophila）发育背腹轴模式形成中发挥活性的背侧（Dorsal）转录因子结合位点。研究发现，与邻近Twist转录因子结合位点协同作用的结合位点，平均可提供约0.5比特的、用于判断侧翼序列中是否存在Twist转录因子结合位点的信息。我们还发现，相较于未考虑侧翼序列特征的检测方法，以侧翼序列信息为条件的背侧结合位点检测器，能更精准地从背景DNA序列中识别出背侧结合位点。