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.

Nucleic Acids Research
|February 1, 2020
PubMed

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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