Local sequence features that influence AP-1 cis-regulatory activity.
Local sequence features that influence AP-1 cis-regulatory activity.
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DOI：
10.1101/gr.226530.117
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发表时间：
2018-03
期刊：
影响因子：
7
通讯作者：
Cohen BA
中科院分区：
文献类型：
--
作者：
Chaudhari HG;Cohen BA
在基因组中，大多数转录因子结合位点(TFBS)没有顺式调节活性，这表明侧翼序列包含区分功能和非功能TFBS的信息。我们询问了激活蛋白1(AP-1)结合位点附近的侧翼序列的作用，这些结合位点位于DNase I超敏位点(DHS)和被注释为增强子的区域。在这些区域，我们发现直接靠近核心基序的序列特征区分了高活性和低活性的AP-1位点。附近的一些特征是与AP-1位点基因相互作用的其他TF的模体。其他特征是AP-1核心基序的延伸，使延伸的位点与多个AP-1结合蛋白的基序匹配。根据这些数据训练的计算模型区分了具有高活性和低活性AP-1位点的序列，并预测了由于AP-1核心位点及其侧翼序列突变而导致的顺式调节活性的变化。我们的结果表明，扩展的AP-1结合位点与其他TF的相邻结合位点一起编码了调控基因组中TFBS活性的部分信息。
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.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
14.9
作者：
Chen X;Ji Z;Webber A;Sharrocks AD
通讯作者：
Sharrocks AD
影响因子：
7
作者：
Kwasnieski JC;Fiore C;Chaudhari HG;Cohen BA
通讯作者：
Cohen BA
影响因子：
14.9
作者：
Maricque BB;Dougherty JD;Cohen BA
通讯作者：
Cohen BA
影响因子：
7
作者：
Inoue, Fumitaka;Kircher, Martin;Shendure, Jay
通讯作者：
Shendure, Jay