Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Syst Biol Med
Impact Factor: 2.385

Chromatin modifications in metabolic disease: Potential mediators of long‐term disease risk

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Metabolic diseases such as obesity and diabetes are complex diseases resulting from multiple genetic and environmental factors, such as diet and activity levels. These factors are well known contributors to the development of metabolic diseases. One manner by which environmental factors can influence metabolic disease progression is through modifications to chromatin. These modifications can lead to altered gene regulatory programs, which alters disease risk. Furthermore, there is evidence that parents exposed to environmental factors can influence the metabolic health of offspring, especially if exposures are during intrauterine growth periods. In this review, we outline the evidence that chromatin modifications are associated with metabolic diseases, including diabetes and obesity. We also consider evidence that these chromatin modifications can lead to long‐term disease risk and contribute to disease risk for future generations.

This article is categorized under:

  • Biological Mechanisms > Metabolism
  • Developmental Biology > Developmental Processes in Health and Disease
  • Physiology > Organismal Responses to Environment
Chromatin modifications associated with “permissive” or “repressive” environments. Modifications to histone tails and DNA methylation are associated with “repressive” states with condensed chromatin or “permissive” state of more accessible chromatin. Red balls, DNA methylation; purple balls, repressive histone modifications; green balls, active histone modifications; yellow globes, histone proteins; blue globes, histone variants
[ Normal View | Magnified View ]
Small RNA‐mediated regulation of gene expression from parental small RNA. Parental small RNAs, in a function independent of the genomic information in sperm, have been shown to transmit phenotypes to offspring. sRNAs can complex to RNA transcripts and induce degradation. Alternatively, sRNAs could bind to actively transcribed RNA in the genome and cause the recruitment of DNA and histone modifying proteins. This could lead to targeted heterochromatin formation in the genome
[ Normal View | Magnified View ]
Intergenerational versus transgenerational inheritance. Epigenetic inheritance in mice can be defined by the number of generations the phenotype penetrates. Maternal effects are changes to the offspring caused as a result of changes in the womb, that is, starvation or altered metabolite intake. The children born after these conditions with altered epigenetic structure are the F0 generation. The F0 generation can also be generated if there is some altering effect, that is, obesogenic diet, that alter the germs cells of an individual. If the phenotype is successfully passed on from the F0 generation to their offspring, the F1 generation, the phenotype is viewed as an intergenerational phenotype. If the phenotype is successfully transferred from the F1 generation to the F2 generation and beyond, the phenotype is viewed as a transgenerational phenotype
[ Normal View | Magnified View ]
Epigenetics and metabolic memory. The phenomenon of metabolic memory is the observation that complications due to metabolic disease can persist even after metabolic disease is mitigated. Epigenetic modifications are an attractive candidate for mediating this phenomenon
[ Normal View | Magnified View ]
Metabolites and chromatin structure. Metabolites are required by many chromatin modifying proteins. S‐adenosyl methionine (SAM) is required by DNA methyltransferases (DNMTs), as well as histone methyltransferases (HMTs) to add a methyl group to DNA or histone tails (Rea et al., ). The metabolites fumartate, succinate and α‐ketogluterate regulate Ten‐eleven translocase (TET) proteins (Klose, Kallin, & Zhang, ). TETs are responsible for the removal of methyl groups from DNA. Flavin adenine dinucleotide (FAD) regulates lysine demethylase (KDM) to regulate the removal of methyl groups from histones. Acetyl‐CoA is required for the addition of acetyl groups to histones by histone acetyl transferases (HATs) (Galdieri & Vancura, ). Nicotinamide adenine dinucleotide (NADH) interacts with Sirtuins to facilitate acetyl group removal by histone deacetylases (HDACs) (Ions et al., ). ATP is a required substrate for serine/threonine kinase (ATM) phosphorylation of histones (Banerjee, Bennion, Goldberg, & Allen, ), which is removed by protein serine/threonine phosphatases (PSPs)
[ Normal View | Magnified View ]
Developmental epigenetic reprograming. There are waves of genome‐wide demethylation followed by the establishment of methylation in primordial germ cells (PGCs) and following fertilization. The vast majority of the genome undergoes this loss of methylation. However, a group of evolutionarily young transposable elements, referred to as “escapees,” avoid the demethylation
[ Normal View | Magnified View ]

Browse by Topic

Developmental Biology > Developmental Processes in Health and Disease
Physiology > Organismal Responses to Environment
Biological Mechanisms > Metabolism

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts

In the Spotlight

Jens Nielsen

Jens Nielsen
is a Professor in the Department of Biology and Biological Engineering at Chalmers University of Technology in Göteborg, Sweden. His research focus is on systems biology of metabolism. The yeast Saccharomyces cerevisiae is the lab’s key organism for experimental research, but they also work with Aspergilli oryzae.

Learn More