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Updated: Dec 29, 2025

Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Complex impact of DNA methylation on transcriptional dysregulation across 22 human cancer types
Zishan Wang1, Jiaqi Yin1, Weiwei Zhou1
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Abstract:
Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) across cancers has not been portrayed. Here, we systematically identified DMTD by integrative analysis of transcriptome, methylome and regulatome across 22 human cancer types. Our results revealed that transcriptional regulation was affected by DNA methylation, involving hundreds of methylation-sensitive TFs (MethTFs). In addition, pan-cancer MethTFs, the regulatory activity of which is generally affected by DNA methylation across cancers, exhibit dominant functional characteristics and regulate several cancer hallmarks. Moreover, pan-cancer MethTFs were found to be affected by DNA methylation in a complex pattern. Finally, we investigated the cooperation among MethTFs and identified a network module that consisted of 43 MethTFs with prognostic potential. In summary, we systematically dissected the transcriptional dysregulation mediated by DNA methylation across cancer types, and our results provide a valuable resource for both epigenetic and transcriptional regulation communities.
Insights
DNA methylation significantly impacts gene regulation, affecting hundreds of methylation-sensitive transcription factors (MethTFs) across cancers. This study maps these DNA methylation-mediated transcriptional dysregulations, revealing key factors with prognostic potential.
Area of Science:
- Epigenetics
- Cancer Biology
- Transcriptional Regulation
Background:
- DNA methylation plays a critical role in transcriptional regulation.
- Understanding DNA methylation-mediated regulatory perturbations is vital for human diseases.
- The global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) in cancer remains largely uncharacterized.
Purpose of the Study:
- To systematically identify and characterize DMTD across 22 human cancer types.
- To investigate the functional characteristics and regulatory patterns of methylation-sensitive transcription factors (MethTFs).
- To identify cooperative networks of MethTFs with prognostic value.
Main Methods:
- Integrative analysis of transcriptome, methylome, and regulatome data.
- Identification of methylation-sensitive transcription factors (MethTFs).
- Network analysis to identify MethTF modules.
Main Results:
- Hundreds of MethTFs were identified, showing transcriptional regulation is affected by DNA methylation.
- Pan-cancer MethTFs exhibit dominant functional characteristics and regulate cancer hallmarks.
- A complex methylation pattern affects pan-cancer MethTFs, with a 43-MethTF module showing prognostic potential.
Conclusions:
- This study systematically dissects DNA methylation-mediated transcriptional dysregulation across diverse cancer types.
- The findings provide a valuable resource for researchers in epigenetics and transcriptional regulation.
- Identified MethTF networks offer potential for cancer diagnostics and therapeutics.
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