%0 Journal Article
%T Crosstalk between transcription factors and microRNAs in human protein interaction network
%A Chen-Ching Lin
%A Ya-Jen Chen
%A Cho-Yi Chen
%A Yen-Jen Oyang
%A Hsueh-Fen Juan
%A Hsuan-Cheng Huang
%J BMC Systems Biology
%D 2012
%I BioMed Central
%R 10.1186/1752-0509-6-18
%X In this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network.Among the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions.Altogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.A gene regulatory network (GRN) is a comprehensive collection of regulatory relationships that controls the global gene expression and the dynamics of protein output in a living cell [1-6]. These regulatory relationships may be derived from different layers in the gene regulatory system. Hence, a GRN can be roughly separated into two major levels: the transcriptional and the post-transcriptional levels.At the transcriptional level, a class of DNA-binding proteins, known as transcription factors (TFs), plays a major role in regulating gene expression. By binding to specific regions of DNA sequences, TFs can control the transcription activities of target genes, thus regulating the production of mRNA transcripts [7-9]. Since it has been widely believed that TFs are the primary regulators of gene expression, previous research on GRNs has mainly focused on the regulatory relationships at the transcriptional level [5,10,11]. However, there is increasing evidence sug
%U http://www.biomedcentral.com/1752-0509/6/18