Coregulation of transcription factors and microRNAs in human transcriptional regulatory network

Abstract

BackgroundMicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators; however, the crosstalk between them still remains unclear.MethodsWe proposed a novel model utilizing functional annotation information to identify significant coregulation between transcriptional and post-transcriptional layers. Based on this model, function-enriched coregulation relationships were discovered and combined into different kinds of functional coregulation networks.ResultsWe found that miRNAs may engage in a wider diversity of biological processes by coordinating with transcription factors, and this kind of cross-layer coregulation may have higher specificity than intra-layer coregulation. In addition, the coregulation networks reveal several types of network motifs, including feed-forward loops and massive upstream crosstalk. Finally, the expression patterns of these coregulation pairs in normal and tumour tissues were analyzed. Different coregulation types show unique expression correlation trends. More importantly, the disruption of coregulation may be associated with cancers.ConclusionOur findings elucidate the combinatorial and cooperative properties of transcription factors and miRNAs regulation, and we proposes that the coordinated regulation may play an important role in many biological processes.

Osteogenic differentiation of human ligament fibroblasts induced by conditioned medium of osteoclast-like cells

“…Each miRNA targets an average of 100-200 genes by binding preferentially to their 3' UTRs by means of partial sequence complementarity (17). miRNAs engage in a wide diversity of biological processes by coordinating with transcription factors, and this kind of crosslayer coregulation may have greater specificity than intra-layer coregulation (18). The current study has suggested that microRNA plays an important role in the osteogenesis of mesenchymal stem cells (19).…”

MicroRNA-Let-7a regulates the function of microglia in inflammation

“…MicroRNAs have been reported to play critical roles in a variety of processes such as neurogenesis (Choi et al, 2008;Kloosterman et al, 2004;Wienholds and Plasterk, 2005). MiRNA-mediated regulation of gene expression has been associated with various important biological processes, including inflammation, apoptosis, angiogenesis, and proliferation (Arora et al, 2013;Chen et al, 2011). Recent studies have shown that miR-155 is able to target microglia M2 phenotype-associated genes, such as that encoding SMAD2, a protein associated with the TGF-β pathway (Louafi et al, 2010).…”

Identification of microRNA-regulated gene networks by expression analysis of target genes

“…However, decades of molecular studies on transcription factors have revealed that their actions are largely combinatorial, i.e., their specific effect-activation or repression of gene expression-is strictly dependent on the local chromatin microenvironment, which in turn is an expression of the combination of multiple factors, such as cell type and a plethora of internal and external stimuli. In this regard, one of the most notable features is that the same transcription factor can activate or repress gene expression and even change binding specificities according to its dynamic interactions with other transcription factors and coactivators (Chen et al 2011). Combinatorial effects multiply the complexity of transcriptionfactor gene regulatory networks, as well as the efforts needed for their dissection.…”