In the genome, most occurrences of transcription factor binding sites (TFBS) have no cis-regulatory activity, which suggests that flanking sequences contain information that distinguishes functional from nonfunctional TFBS. We interrogated the role of flanking sequences near Activator Protein 1 (AP-1) binding sites that reside in DNase I Hypersensitive Sites (DHS) and regions annotated as Enhancers. In these regions, we found that sequence features directly adjacent to the core motif distinguish high from low activity AP-1 sites. Some nearby features are motifs for other TFs that genetically interact with the AP-1 site. Other features are extensions of the AP-1 core motif, which cause the extended sites to match motifs of multiple AP-1 binding proteins. Computational models trained on these data distinguish between sequences with high and low activity AP-1 sites and also predict changes in cis-regulatory activity due to mutations in AP-1 core sites and their flanking sequences. Our results suggest that extended AP-1 binding sites, together with adjacent binding sites for additional TFs, encode part of the information that governs TFBS activity in the genome.

在基因组中，大多数转录因子结合位点（TFBS）都没有顺式-调节活性，这表明侧翼序列包含区分功能性和非功能性TFBS的信息。我们询问了位于DNase I超敏位点（DHS）和标注为增强子的区域的激活蛋白1（AP-1）结合位点附近的侧翼序列的作用。在这些区域中，我们发现与核心基序直接相邻的序列特征将高活性和低活性AP-1位点区分开。附近的一些特征是与AP-1位点遗传相互作用的其他TF的基序。其他特征是AP-1核心基序的延伸，这导致延伸的位点与多个AP-1结合蛋白的基序匹配。在这些数据上训练的计算模型可以区分具有高活性和低活性AP-1位点的序列，还可以预测顺式的变化AP-1核心位点及其侧翼序列中的突变引起的调节活性。我们的结果表明，扩展的AP-1结合位点以及与其他TF相邻的结合位点，可编码控制基因组中TFBS活性的部分信息。