Theme 4: Toxicology Flashcards
What is the definition of epigenetics?
The study of heritable changes in gene expression that do not involve changes to the DNA sequence.
Name three key mechanisms of epigenetic regulation.
- DNA methylation
- Histone modifications
- RNA interference (RNAi).
What is the role of DNA methylation in gene expression?
DNA methylation typically represses gene expression by preventing transcription factors from binding to DNA.
How does histone acetylation affect gene expression?
Histone acetylation relaxes chromatin structure, making DNA more accessible to transcription factors and increasing gene expression.
How does the peloric variant of toadflax (Linaria) demonstrate epigenetics?
It is caused by DNA methylation rather than genetic mutation, leading to heritable changes in flower symmetry.
What causes queen and worker bees to have different phenotypes despite identical DNA?
Differences in royal jelly consumption alter DNA methylation patterns, affecting gene expression.
Explain the mouse agouti model in relation to epigenetics.
Coat colour and obesity in genetically identical mice depend on methylation at the Agouti gene; maternal diet can influence these traits.
What was the significance of the Dutch Hunger Winter study in epigenetics?
It demonstrated that prenatal famine exposure led to changes in DNA methylation that persisted into adulthood and affected health outcomes.
What is genomic imprinting?
An epigenetic phenomenon where only one allele (maternal or paternal) is expressed while the other is silenced.
What is an example of a disease caused by errors in genomic imprinting?
Prader-Willi Syndrome (paternal deletion) and Angelman Syndrome (maternal deletion).
How can Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) develop from the same genetic mutation?
AS is a classic example of genomic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced.
Prader-Willi syndrome (PWS), is caused by a mutation of the paternally inherited gene while the maternal copy, which may be of normal sequence,is imprinted and therefore silenced.
How does X-chromosome inactivation occur in females?
One X chromosome is randomly inactivated via DNA methylation and histone modifications to balance gene expression.
How does exposure to Bisphenol A (BPA) affect the epigenome in mice?
BPA reduces DNA methylation at the Agouti gene, leading to an increased proportion of yellow, obese offspring in the mouse model.
What are transgenerational epigenetic effects, and what chemical is known to cause them?
Changes in gene expression passed down generations without altering DNA sequence; Vinclozulin (fungicide) is known to cause these effects.
How does Vinclozulin cause transgenerational effects?
It disrupts DNA methylation patterns in germ cells, leading to inherited changes in sperm epigenetics across generations.
How does DEHP exposure affect epigenetics?
It alters DNA methylation of imprinted genes in germ cells, affecting future generations.
How do HDAC inhibitors act as developmental toxicants?
They interfere with chromatin compaction, altering gene expression and leading to developmental defects.
How does DNA hypomethylation contribute to cancer?
Hypomethylation activates oncogenes and increases genomic instability by allowing transposable elements to move.
How does DNA hypermethylation contribute to cancer?
It silences tumor suppressor genes, preventing them from stopping uncontrolled cell growth.
What are three types of epigenetic modifications found in cancer?
- DNA methylation changes
- Histone modification changes
- Deregulation of miRNAs.
What is an example of an epigenetic carcinogen, and how does it affect gene expression?
Arsenic; it alters DNA methylation patterns, leading to silencing of tumor suppressor genes.
Name two classes of epigenetic drugs used in cancer treatment and their targets.
- DNA methylation inhibitors (e.g., 5-Aza-CR, 5-Aza-CdR) – Reactivate silenced tumor suppressor genes.
- Histone deacetylase (HDAC) inhibitors (e.g., Vorinostat) – Increase gene expression by preventing chromatin compaction.
How do CRISPR-based tools have potential in epigenetic therapy?
CRISPR/dCas9 systems can be used to edit epigenetic marks, such as DNA methylation, at specific genomic sites.
How can nutrition influence epigenetics?
Nutrients like folate, B12, and choline act as methyl donors, affecting DNA methylation patterns and gene expression.
