Wang Yao, Wang Rui, Jin Victor X
Departments of Molecular Medicine and Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA,
School of Chemical and Environment Science, Shaanxi University of Technology, Hanzhong, Shaanxi 723000, China,
Int J Comput Biol Drug Des. 2016;9(1-2):25-53. doi: 10.1504/IJCBDD.2016.074990.
The TCF7L2 transcription factor (TF) is a member of Wnt signalling pathway, and may influence transcription of several genes by binding to distinct regulatory regions. Genome-wide studies have identified thousands of TCF7L2 binding sites and have revealed some associated TF partners. However, there is still a large uncharted region in the hierarchical regulatory network for TCF7L2 and the partner TFs in MCF7 cells. We analysed ChIP-seq data by searching for motifs in the enriched peak region based on TF-specific position weight matrix (PWM). We found association of FOXO1 and CAD with up-regulated genes, AP2α, PBF and AP1 with down-regulated genes. TCF7L2 and GATA3 were found to be associated with both up and down-regulated genes. Our study uncovers new TCF7L2 associated regulatory networks by mining ChIP-seq data in MCF7 cell, which may contribute to further study of the mechanisms related to Wnt pathway in breast cancer or other diseases.
转录因子TCF7L2是Wnt信号通路的成员之一，它可能通过与不同的调控区域结合来影响多个基因的转录。全基因组研究已经鉴定出数千个TCF7L2结合位点，并揭示了一些相关的转录因子伙伴。然而，在MCF7细胞中，TCF7L2及其伙伴转录因子的层级调控网络仍有很大一部分未知区域。我们通过基于转录因子特异性位置权重矩阵（PWM）在富集峰区域搜索基序来分析ChIP-seq数据。我们发现FOXO1和CAD与上调基因相关，AP2α、PBF和AP1与下调基因相关。发现TCF7L2和GATA3与上调和下调基因均相关。我们的研究通过挖掘MCF7细胞中的ChIP-seq数据，揭示了新的TCF7L2相关调控网络，这可能有助于进一步研究乳腺癌或其他疾病中与Wnt通路相关的机制。
