Computational Analysis of Tissue-specific Combinatorial Gene Regulation: Predicting Interaction Between Transcription Factors in Human Tissues

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2006 Sep 20

PMID 16982645

Citations 94

Authors

Xueping Yu

Jimmy Lin

Donald J Zack

Jiang Qian

Affiliations

Soon will be listed here.

Abstract

Tissue-specific gene expression is generally regulated by more than a single transcription factor (TF). Multiple TFs work in concert to achieve tissue specificity. In order to explore these complex TF interaction networks, we performed a large-scale analysis of TF interactions for 30 human tissues. We first identified tissue-specific genes for 30 tissues based on gene expression databases. We then evaluated the relationships between TFs using the relative position and co-occurrence of their binding sites in the promoters of tissue-specific genes. The predicted TF-TF interactions were validated by both known protein-protein interactions and co-expression of their target genes. We found that our predictions are enriched in known protein-protein interactions (>80 times that of random expectation). In addition, we found that the target genes show the highest co-expression in the tissue of interest. Our findings demonstrate that non-tissue specific TFs play a large role in regulation of tissue-specific genes. Furthermore, they show that individual TFs can contribute to tissue specificity in different tissues by interacting with distinct TF partners. Lastly, we identified several tissue-specific TF clusters that may play important roles in tissue-specific gene regulation.

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