Related Experiment Video

Updated: May 15, 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

MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma

Jessica Charlet1, Marianna Szemes, Karim T A Malik

  • 1School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.

Molecular Carcinogenesis
|January 3, 2013
PubMed

Insights

MYCN interacts with DNA methyltransferases in neuroblastoma, but does not drive tumor suppressor gene hypermethylation. This finding suggests MYCN is not critical for epigenetic repression in neuroblastoma.

Area of Science:

  • Neuro-oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Neuroblastoma frequently exhibits amplified MYCN and hypermethylation of tumor suppressor genes like RASSF1A.
  • The MYC proto-oncogene's association with DNA methyltransferases suggests MYCN might induce hypermethylation in neuroblastoma.

Purpose of the Study:

  • To investigate the mechanistic role of MYCN in the DNA hypermethylation of tumor suppressor genes in neuroblastoma.
  • To determine if MYCN interacts with DNA methyltransferases and influences gene methylation patterns.

Main Methods:

  • Co-immunoprecipitation and Chromatin Immunoprecipitation (ChIP) assays to detect MYCN-DNA methyltransferase interactions.
  • MYCN knockdown and overexpression systems in neuroblastoma cell lines.
  • Candidate gene and genome-wide methylation assays.

Main Results:

  • MYCN was found to interact with DNA methyltransferases and be recruited to the RASSF1A promoter region.
  • Long-term MYCN silencing resulted in minimal DNA methylation loss at the RASSF1A promoter in MYCN-amplified neuroblastoma cells.
  • MYCN overexpression did not induce significant DNA methylation changes.

Conclusions:

  • MYCN interacts with DNA methyltransferases but is not the critical driver of DNA hypermethylation in neuroblastoma.
  • The epigenetic repression of tumor suppressor genes in neuroblastoma likely involves mechanisms independent of MYCN's direct role in DNA methylation induction.
Keywords:
DNA hypermethylationMYCNepigeneticsneuroblastoma

More Related Videos

Zebrafish Model of Neuroblastoma Metastasis05:20

Zebrafish Model of Neuroblastoma Metastasis

Published on: March 14, 2021

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

Related Concept Videos

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.
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...
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 daughter...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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 cells are...
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...