Related Experiment Video

Updated: Mar 30, 2026

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
08:37

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer

Published on: November 15, 2024

852

Hepatic DNA hydroxymethylation is site-specifically altered by chronic alcohol consumption and aging

Stephanie A Tammen1,2, Lara K Park1,2, Gregory G Dolnikowski1,2

  • 1Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

European Journal of Nutrition
|November 19, 2015
PubMed
Abstract

Insights

Alcohol consumption significantly alters DNA hydroxymethylation patterns, especially in younger mice, impacting gene expression related to liver function and potentially contributing to cancer risk. These site-specific epigenetic changes are crucial in the liver

Area of Science:

  • Epigenetics
  • Genomics
  • Hepatology

Background:

  • Global DNA hydroxymethylation decreases in human cancers, including hepatocellular carcinoma.
  • Chronic alcohol consumption and aging are linked to reduced DNA hydroxymethylation.
  • Gene-specific epigenetic modifications can influence transcription and contribute to carcinogenesis.

Purpose of the Study:

  • To investigate genome-wide, site-specific changes in hepatic hydroxymethylation.
  • To determine the impact of chronic alcohol consumption and aging on DNA hydroxymethylation patterns.
  • To correlate hydroxymethylation changes with gene expression in the liver.

Main Methods:

  • Utilized a mouse model with young and old male C57Bl/6 mice.
  • Administered ethanol-containing or control liquid diets for five weeks.
  • Employed hydroxymethyl DNA immunoprecipitation arrays to analyze genomic and gene-specific hydroxymethylation.

Main Results:

  • Alcohol perturbed hydroxymethylation more in young mice (431 regions) than old mice (189 regions).
  • Increased hydroxymethylation and mRNA expression of Nr3c1 (glucocorticoid receptor) in young alcohol-fed mice.
  • Aging altered hydroxymethylation (331 regions), but alcohol attenuated this; decreased hydroxymethylation near Lepr (leptin receptor) correlated with reduced transcription.

Conclusions:

  • DNA hydroxymethylation is site-specific and not random.
  • Epigenetic alterations in hydroxymethylation are implicated in the liver's response to alcohol and aging.
  • Changes in Nr3c1 and Lepr hydroxymethylation may contribute to hepatic lipid homeostasis disruption and hepatosteatosis, potentially creating a carcinogenic environment.
Keywords:
AgingAlcoholDNA hydroxymethylationLiverhmeDIP-Chip

More Related Videos

Methodology for Accurate Detection of Mitochondrial DNA Methylation12:11

Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

14.0K
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

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...
4.2K
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.
34.3K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.9K
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.9K
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
335
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
256