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Updated: Jun 21, 2025
Analyzing Tumor Gene Expression Factors with the CorExplorer Web Portal
Published on: October 11, 2019
A large-scale cancer-specific protein-DNA interaction network
Yunwei Lu1, Anna Berenson1,2, Ryan Lane1
1Biology Department, Boston University, Boston, MA, USA.
Abstract:
Cancer development and progression are generally associated with gene dysregulation, often resulting from changes in the transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network, as well as an extensive promoter clone resource for future studies. Highly connected TFs bind to promoters of genes associated with either good or poor cancer prognosis, suggesting that strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene-targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activators or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF ESR1 in DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study broadens our knowledge of the TFs involved in cancer gene regulation and provides a valuable resource for future studies and therapeutics.
Insights
This study maps cancer gene transcription factor (TF) interactions, revealing TFs linked to patient outcomes. It identifies therapeutic targets, particularly for repressing oncogenes, and explores TF structural roles in gene regulation.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
- Bioinformatics
Background:
- Gene dysregulation, driven by transcription factor (TF) alterations, is central to cancer development.
- Identifying key TFs in cancer gene regulation is crucial for developing novel therapeutic strategies.
- Understanding TF-DNA interactions provides a foundation for targeted cancer treatments.
Purpose of the Study:
- To construct a large-scale cancer gene TF-DNA interaction network.
- To identify potential therapeutic targets by analyzing TF roles in cancer prognosis.
- To investigate the functional significance of intrinsically disordered regions in cancer-related TFs.
Main Methods:
- Development of a comprehensive TF-DNA interaction network using bioinformatics approaches.
- Analysis of TF connectivity in relation to cancer gene promoters and patient prognosis.
- Experimental investigation of intrinsically disordered regions in the ESR1 transcription factor.
Main Results:
- A large-scale network revealed highly connected TFs associated with both favorable and unfavorable cancer prognoses.
- Half of tested oncogenes showed potential for repression via modulation of specific activators or bifunctional TFs.
- Intrinsically disordered regions in ESR1 demonstrated complex roles in DNA binding and transcriptional activity.
Conclusions:
- The study provides a valuable resource for understanding TFs in cancer gene regulation.
- Findings suggest therapeutic strategies targeting gene expression balance may be complex but offer oncogene repression potential.
- Insights into TF structure-function relationships, like those in ESR1, can inform future drug development.
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