Related Experiment Video

Updated: May 13, 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

NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink

Olesya A Ulanovskaya1, Andrea M Zuhl, Benjamin F Cravatt

  • 1The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.

Nature Chemical Biology
|March 5, 2013
PubMed

Insights

Nicotinamide N-methyltransferase (NNMT) overexpression in cancer depletes methyl groups, altering cell epigenetics. This metabolic disruption promotes tumor growth by affecting gene expression and protein methylation.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Epigenetics

Background:

  • Nicotinamide N-methyltransferase (NNMT) is frequently overexpressed in various human cancers.
  • The precise mechanism by which NNMT contributes to tumorigenesis remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanistic link between NNMT overexpression and cancer development.
  • To investigate the impact of NNMT on cellular methylation potential and epigenetic modifications.

Main Methods:

  • Metabolomic analysis was employed to study the metabolic consequences of NNMT activity.
  • Changes in histone and protein methylation were assessed in NNMT-expressing cancer cells.

Main Results:

  • NNMT was found to consume methyl units from S-adenosyl methionine, producing 1-methylnicotinamide.
  • NNMT overexpression led to hypomethylated histones and other proteins in cancer cells.
  • Heightened expression of protumorigenic genes was observed in conjunction with NNMT activity.

Conclusions:

  • NNMT deregulation directly impacts the cellular methylation landscape.
  • NNMT contributes to tumorigenesis by altering epigenetic states and promoting protumorigenic gene expression.

More Related Videos

Methyl-binding DNA capture Sequencing for Patient Tissues08:40

Methyl-binding DNA capture Sequencing for Patient Tissues

Published on: October 31, 2016

Methylated DNA Immunoprecipitation21:24

Methylated DNA Immunoprecipitation

Published on: January 2, 2009

Related Concept Videos

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...
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.
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
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...