title: Understanding the combinatorial action of transcription factors and microRNA regulation from regions of open chromatin.
abstract: Transcriptional regulatory cascades are always triggered through the combinatorial interplay between transcription factors (TFs) and microRNAs (miRNAs) in eukaryotes. However, it is still a very substantial undertaking to dynamically profile their coordinated actions. In this work, we compared the differences in TFBS numbers between miRNA targets and non-targets, and found that miRNA targets tend to have more TFBS numbers. With the attempt to comprehensively understand the combinatorial action of TF and miRNA regulation from regions of open chromatin, we retrieved recently published DNase I hypersensitive sites (DHSs) across different human cell lines. The result showed that the differences are more statistically significant in DHS regions than non-DHS regions. Next, we trained classifiers for miRNA targets and non-targets. The result showed that TFBSs located in DHS regions achieved a competitive performance when discriminating miRNA targets and non-targets, whereas the performance of classifiers using TFBSs located in non-DHS regions is close to that of a random classifier. After the DHSs were divided into intergenic, transcription start sites (TSSs) and gene body DHS regions based on their genomic locations, only TFBSs located in TSS DHS regions provided a competitive performance. Our results provide us a clue that the coordinated activity of miRNAs and TFs describing the mechanism of gene expression control should be examined in a dynamic perspective.
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute of Estuarine and Coastal Research, East China Normal University, Shanghai, 200062, P. R. China.
authors.forename: Guantao
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute of Estuarine and Coastal Research, East China Normal University, Shanghai, 200062, P. R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory for Genetic Research of Bone and Joint Disease, No. 1 Shuaifuyuan, Beijing, 100730, P. R. China. ddong.ecnu@gmail.com wuzh3000@126.com and Central laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, P. R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute of Estuarine and Coastal Research, East China Normal University, Shanghai, 200062, P. R. China and Beijing Key Laboratory for Genetic Research of Bone and Joint Disease, No. 1 Shuaifuyuan, Beijing, 100730, P. R. China. ddong.ecnu@gmail.com wuzh3000@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D060388:Support Vector Machine; D014157:Transcription Factors / Q000502:physiology*; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors