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This article is part of the supplement: The 2010 International Conference on Bioinformatics and Computational Biology (BIOCOMP 2010): Genomics

Open Access Highly Accessed Research article

Functional complementation between transcriptional methylation regulation and post-transcriptional microRNA regulation in the human genome

Zhixi Su12, Junfeng Xia1 and Zhongming Zhao134*

  • * Corresponding author: Zhongming Zhao

  • † Equal contributors

Author Affiliations

1 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

2 MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai 200433, China

3 Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

4 Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

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BMC Genomics 2011, 12(Suppl 5):S15  doi:10.1186/1471-2164-12-S5-S15

Published: 23 December 2011

Abstract

Background

DNA methylation in the 5' promoter regions of genes and microRNA (miRNA) regulation at the 3' untranslated regions (UTRs) are two major epigenetic regulation mechanisms in most eukaryotes. Both DNA methylation and miRNA regulation can suppress gene expression and their corresponding protein product; thus, they play critical roles in cellular processes. Although there have been numerous investigations of gene regulation by methylation changes and miRNAs, there is no systematic genome-wide examination of their coordinated effects in any organism.

Results

In this study, we investigated the relationship between promoter methylation at the transcription level and miRNA regulation at the post-transcription level by taking advantage of recently released human methylome data and high quality miRNA and other gene annotation data. We found methylation level in the promoter regions and expression level was negatively correlated. Then, we showed that miRNAs tended to target the genes with a low DNA methylation level in their promoter regions. We further demonstrated that this observed pattern was not attributed to the gene expression level, expression broadness, or the number of transcription factor binding sites. Interestingly, we found miRNA target sites were significantly enriched in the genes located in differentially methylated regions or partially methylated domains. Finally, we explored the features of DNA methylation and miRNA regulation in cancer genes and found cancer genes tended to have low methylation level and more miRNA target sites.

Conclusion

This is the first genome-wide investigation of the combined regulation of gene expression. Our results supported a complementary regulation between DNA methylation (transcriptional level) and miRNA function (post-transcriptional level) in the human genome. The results were helpful for our understanding of the evolutionary forces towards organisms' complexity beyond traditional sequence level investigation.