DNA methylation and histone H3-K9 modifications contribute to MUC17 expression

Sho Kitamoto1, Norishige Yamada, Seiya Yokoyama

  • 1Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Glycobiology
|October 8, 2010
PubMed

Insights

Epigenetic regulation of MUC17, including DNA methylation and histone modification, impacts its expression in pancreatic cancer. MUC17 promoter hypomethylation may serve as a novel diagnostic marker for pancreatic ductal adenocarcinoma (PDAC).

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • MUC17 glycoprotein is a membrane-associated mucin primarily found in the digestive tract.
  • MUC17 expression is potentially linked to the malignancy of pancreatic ductal adenocarcinomas (PDACs).

Purpose of the Study:

  • To investigate the epigenetic regulation of MUC17 gene expression.
  • To explore the role of DNA methylation, histone modification, and microRNA (miRNA) in MUC17 expression.
  • To assess the potential of MUC17 promoter hypomethylation as a diagnostic marker for PDAC.

Main Methods:

  • Analysis of DNA methylation levels near the MUC17 transcriptional start site in cancer cell lines.
  • Assessment of Histone H3-K9 modification status in relation to MUC17 expression.
  • MicroRNA (miRNA) microarray analysis to identify potential miRNA regulators.

Main Results:

  • High DNA methylation levels were observed in MUC17-negative cell lines (e.g., PANC1), while low levels were found in MUC17-positive cell lines (e.g., AsPC-1).
  • Histone H3-K9 modification status correlated with MUC17 expression.
  • Hypomethylation of the MUC17 promoter was identified in PDAC patients, suggesting its potential as a diagnostic marker.
  • Five potential miRNA candidates were identified, indicating possible post-transcriptional regulation of MUC17 by miRNAs.

Conclusions:

  • DNA methylation and Histone H3-K9 modification in the 5' flanking region critically regulate MUC17 expression.
  • MUC17 promoter hypomethylation presents a novel epigenetic marker for PDAC diagnosis.
  • Understanding MUC17's epigenetic changes may aid in diagnosing carcinogenic risk and predicting cancer patient outcomes.

Related Concept Videos

Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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.
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...
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...