Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Jul;132(1):72-79. doi: 10.1016/j.oooo.2021.01.002. Epub 2021 Jan 9.
The objective of this study was identification of the transcription factor binding sites (TFBS) in the promoter of HOX genes and elucidation of the comprehensive interaction of transcription factors (TFs)/genes with HOX.
Promoter sequences of HOXA3, HOXA5, HOXA9, HOXA10, HOXA13, HOXB5, HOXC10, HOXC12, and HOXD10 were analyzed to predict the TFBS and their targets using TRANSFAC, TRRUST, and Harmonizome. Functional analysis of the processed data sets was carried out using DAVID and GATHER gene annotation tools. A network of regulatory interactions was constructed using NetworkAnalyst and a comprehensive illustration of the TF-gene network was constructed with HOX as a central hub using the Encyclopedia of DNA Elements chromatin immunoprecipitation sequencing data. Further, the enriched network was constructed to elucidate the roles of these genes in the various pathways.
Binding sites for E2F1, HNF3α, SP3, and KLF6 were common to promoter regions of all of the HOX genes. The functional annotation and pathway analysis elucidated the regulatory activity of a distinct set of TF-genes in interaction with HOX. A P value ≤.05 and false discovery rate ≤0.01 were considered statistically significant.
We have confirmed that the predicted TFBSs in the HOX gene promoters function in transcriptional regulation by modulating target gene activity. TF-gene interactions are crucial to understanding oral carcinogenesis.
本研究旨在鉴定 HOX 基因启动子中的转录因子结合位点（TFBS），并阐明转录因子（TF）/基因与 HOX 的综合相互作用。
分析 HOXA3、HOXA5、HOXA9、HOXA10、HOXA13、HOXB5、HOXC10、HOXC12 和 HOXD10 的启动子序列，使用 TRANSFAC、TRRUST 和 Harmonizome 预测 TFBS 及其靶标。使用 DAVID 和 GATHER 基因注释工具对处理后的数据进行功能分析。使用 NetworkAnalyst 构建调控相互作用网络，并使用 ENCODE DNA 元件染色质免疫沉淀测序数据以 HOX 作为中心枢纽构建 TF-基因网络的综合示意图。此外，构建富集网络以阐明这些基因在各种途径中的作用。
E2F1、HNF3α、SP3 和 KLF6 的结合位点在所有 HOX 基因的启动子区域都很常见。功能注释和通路分析阐明了一组特定的 TF-基因与 HOX 相互作用的调节活性。P 值≤.05 和错误发现率≤0.01 被认为具有统计学意义。
我们已经证实，HOX 基因启动子中预测的 TFBS 通过调节靶基因活性在转录调控中起作用。TF-基因相互作用对于理解口腔癌发生至关重要。
