Related Experiment Video

Updated: Apr 19, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

3.3K

RFTS-deleted DNMT1 enhances tumorigenicity with focal hypermethylation and global hypomethylation

Bo-Kuan Wu1, Szu-Chieh Mei, Charles Brenner

  • 1a Department of Biochemistry; Carver College of Medicine ; University of Iowa ; Iowa City , IA USA.

Cell Cycle (Georgetown, Tex.)
|December 9, 2014
PubMed

Insights

The RFTS domain of DNMT1 is crucial for cancer's epigenetic changes. Its deletion causes both hypermethylation and hypomethylation, driving malignant transformation.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Epigenetic alterations, specifically site-specific hypermethylation and genome-wide hypomethylation, are hallmarks of cancer.
  • The molecular mechanisms underlying these paradoxical DNA methylation changes are not fully understood.
  • DNA methyltransferase 1 (DNMT1) is frequently dysregulated in tumors, but its precise role in these epigenetic shifts is complex.

Purpose of the Study:

  • To investigate the role of the Replication Foci Targeting Sequence (RFTS) domain of DNMT1 in regulating DNA methylation during malignant transformation.
  • To determine if deletion of the RFTS domain alters DNMT1 function and contributes to cancer-associated epigenetic changes.

Main Methods:

  • Ectopic expression of full-length DNMT1 and a DNMT1 variant lacking the RFTS domain (DNMT1-ΔRFTS) in cells.
  • Analysis of DNA methylation patterns at specific gene promoters (DAPK, DUOX1) and repetitive elements (SAT2).
  • Assessment of chromatin structure, gene expression, and malignant transformation phenotypes.

Main Results:

  • Ectopic expression of DNMT1-ΔRFTS led to increased malignant transformation compared to full-length DNMT1.
  • DNMT1-ΔRFTS enhanced promoter hypermethylation and silenced tumor suppressor genes DAPK and DUOX1.
  • Deletion of RFTS impaired DNMT1 association with SAT2 repeats, causing demethylation at these sites and globally.

Conclusions:

  • The RFTS domain of DNMT1 is essential for maintaining normal DNA methylation patterns during malignant transformation.
  • DNMT1-ΔRFTS acts as a single factor capable of inducing both focal hypermethylation and global hypomethylation, mimicking key epigenetic features of cancer.
  • The RFTS domain represents a potential therapeutic target for reversing cancer-associated epigenetic dysregulation.
Keywords:
COSMIC, catalog of somatic mutation in cancerDNA methylationDNMT1DNMT1, DNA methyltransferase 1HELP, HpaII tiny fragment enrichment by ligation-mediated PCRKEGG, Kyoto Encyclopedia of Genes and GenomesRFTS domainRFTS, replication foci targeting sequenceTSGs, tumor suppressor geneschromatintumorigenicity

More Related Videos

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

10.4K
In vitro tRNA Methylation Assay with the Entamoeba histolytica DNA and tRNA Methyltransferase Dnmt2 Ehmeth Enzyme12:36

In vitro tRNA Methylation Assay with the Entamoeba histolytica DNA and tRNA Methyltransferase Dnmt2 Ehmeth Enzyme

Published on: October 19, 2010

14.9K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
4.3K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.6K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.4K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
6.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K