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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

Distributions of enriched biological processes for different regulation types. (A) Distributions for TF-involving regulation: individual TFs, TF-TF pairs, and TF-miRNA pairs. (B) Distributions for miRNA-involving regulation: individual miRNAs, miRNA-miRNA pairs, and TF-miRNA pairs. Note that the same TF-miRNA line are drawn in both (A) and (B) for comparison.
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Figure 3: Distributions of enriched biological processes for different regulation types. (A) Distributions for TF-involving regulation: individual TFs, TF-TF pairs, and TF-miRNA pairs. (B) Distributions for miRNA-involving regulation: individual miRNAs, miRNA-miRNA pairs, and TF-miRNA pairs. Note that the same TF-miRNA line are drawn in both (A) and (B) for comparison.

Mentions: The distributions of different regulation types were grouped into two diagrams for comparing. Figure 3A shows distributions of individual TF regulation and TF-TF coregulation. The two distributions look similar; however, two biological processes, pigmentation and reproductive process, emerge when it comes to TF-miRNA coregulation, implying that the two biological processes may be the typical processes in which TFs should coordinate with miRNAs to control the expression programs.


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

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

Distributions of enriched biological processes for different regulation types. (A) Distributions for TF-involving regulation: individual TFs, TF-TF pairs, and TF-miRNA pairs. (B) Distributions for miRNA-involving regulation: individual miRNAs, miRNA-miRNA pairs, and TF-miRNA pairs. Note that the same TF-miRNA line are drawn in both (A) and (B) for comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Distributions of enriched biological processes for different regulation types. (A) Distributions for TF-involving regulation: individual TFs, TF-TF pairs, and TF-miRNA pairs. (B) Distributions for miRNA-involving regulation: individual miRNAs, miRNA-miRNA pairs, and TF-miRNA pairs. Note that the same TF-miRNA line are drawn in both (A) and (B) for comparison.
Mentions: The distributions of different regulation types were grouped into two diagrams for comparing. Figure 3A shows distributions of individual TF regulation and TF-TF coregulation. The two distributions look similar; however, two biological processes, pigmentation and reproductive process, emerge when it comes to TF-miRNA coregulation, implying that the two biological processes may be the typical processes in which TFs should coordinate with miRNAs to control the expression programs.

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