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Coregulation of transcription factors and microRNAs in human transcriptional regulatory network.

Chen CY, Chen ST, Fuh CS, Juan HF, Huang HC - BMC Bioinformatics (2011)

Bottom Line: We 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.More importantly, the disruption of coregulation may be associated with cancers.Our 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan. joeychen@gate.sinica.edu.tw

ABSTRACT

Background: MicroRNAs (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.

Methods: We 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.

Results: We 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.

Conclusion: Our 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.

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Related in: MedlinePlus

Example workflow for constructing functional coregulation network. For each coregulation pair, a function linkage was established if a GO term enriched in their shared targets. The coregulation network was generated based on these function linkages. Nodes represent regulators, and edge represents GO terms, marked with different colours.
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Figure 2: Example workflow for constructing functional coregulation network. For each coregulation pair, a function linkage was established if a GO term enriched in their shared targets. The coregulation network was generated based on these function linkages. Nodes represent regulators, and edge represents GO terms, marked with different colours.

Mentions: For each function-enriched coregulation pair, Fisher’s Exact Test following FDR correction were conducted to identify enriched GO terms. Similarly, we only focused on the second level terms in biological process namespace. A functional linkage was established if a GO term overrepresented in the shared targets of a coregulation pair, implying that the two paired regulators may function coordinately in the specific biological process. Based on these linkages, we further constructed the functional coregulation networks (Figure 2). In order to investigate the specificity of coregulation relationships and provide a global view, only those linkages with relatively high significance that passed FDR-BL correction [17] were used to construct the networks.


Coregulation of transcription factors and microRNAs in human transcriptional regulatory network.

Chen CY, Chen ST, Fuh CS, Juan HF, Huang HC - BMC Bioinformatics (2011)

Example workflow for constructing functional coregulation network. For each coregulation pair, a function linkage was established if a GO term enriched in their shared targets. The coregulation network was generated based on these function linkages. Nodes represent regulators, and edge represents GO terms, marked with different colours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044298&req=5

Figure 2: Example workflow for constructing functional coregulation network. For each coregulation pair, a function linkage was established if a GO term enriched in their shared targets. The coregulation network was generated based on these function linkages. Nodes represent regulators, and edge represents GO terms, marked with different colours.
Mentions: For each function-enriched coregulation pair, Fisher’s Exact Test following FDR correction were conducted to identify enriched GO terms. Similarly, we only focused on the second level terms in biological process namespace. A functional linkage was established if a GO term overrepresented in the shared targets of a coregulation pair, implying that the two paired regulators may function coordinately in the specific biological process. Based on these linkages, we further constructed the functional coregulation networks (Figure 2). In order to investigate the specificity of coregulation relationships and provide a global view, only those linkages with relatively high significance that passed FDR-BL correction [17] were used to construct the networks.

Bottom Line: We 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.More importantly, the disruption of coregulation may be associated with cancers.Our 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan. joeychen@gate.sinica.edu.tw

ABSTRACT

Background: MicroRNAs (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.

Methods: We 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.

Results: We 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.

Conclusion: Our 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.

Show MeSH
Related in: MedlinePlus