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Updated: Jun 30, 2026

Targeted DNA Methylation Analysis by Next-generation Sequencing
08:38

Targeted DNA Methylation Analysis by Next-generation Sequencing

Published on: February 24, 2015

CpG methylation is maintained in human cancer cells lacking DNMT1

I Rhee1, K W Jair, R W Yen

  • 1The Johns Hopkins Oncology Center, and Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Nature
|May 9, 2000
PubMed

Insights

DNA methyltransferase 1 (DNMT1) is not solely responsible for genomic methylation in human cancer cells. Other enzymes maintain methylation, indicating DNMT1 has regional specificity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Aberrant DNA methylation, particularly hypermethylation, is a hallmark of cancer, often leading to the silencing of tumor suppressor genes.
  • The precise mechanisms driving this abnormal methylation are not fully understood, with DNA methyltransferase 1 (DNMT1) being the presumed primary enzyme responsible for genomic methylation.

Purpose of the Study:

  • To investigate the role of DNMT1 in maintaining global genomic methylation and specific gene methylation in human colorectal carcinoma cells.
  • To determine if DNMT1 is the sole enzyme responsible for aberrant methylation in cancer.

Main Methods:

  • Disruption of the DNMT1 gene in human colorectal carcinoma cells using homologous recombination.
  • Measurement of cellular DNA methyltransferase activity.
  • Analysis of overall genomic methylation levels.
  • Assessment of methylation status at specific loci, including juxtacentromeric satellites and the p16INK4a tumor suppressor gene.

Main Results:

  • Cells lacking DNMT1 showed significantly reduced cellular DNA methyltransferase activity.
  • Overall genomic methylation decreased by only 20% in DNMT1-deficient cells.
  • Juxtacentromeric satellite regions were significantly demethylated, but most analyzed loci, including p16INK4a, remained fully methylated and silenced.
  • These findings suggest the presence of alternative methylating activities in human cells.

Conclusions:

  • DNMT1 exhibits unexpected regional specificity in its methylation activity within human cells.
  • Enzymes other than DNMT1 play a crucial role in maintaining the methylation status of the majority of the human genome, even in the context of cancer.

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