Chapter 03: Epigenetics and Disease

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Questions and Answers

What is the primary effect of DNA methylation on gene expression?

It enhances transcription of mRNA.

It inhibits transcription of mRNA. (correct)

It prevents chromatin condensation.

It increases the binding of transcription proteins.

Which epigenetic mechanism is best understood according to recent research?

Noncoding RNAs

DNA methylation (correct)

Chromatin remodeling

Histone modifications

What typically triggers the loss of DNA methylation in fertilized cells?

Presence of DNA methyltransferases

Implantation in the uterus

Environmental factors

The fertilization process itself (correct)

How do environmental factors influence epigenetic modifications?

They can lead to the attachment or removal of methyl groups. Signup and view all the answers

Which type of genes are referred to as housekeeping genes?

Genes necessary for cell function and maintenance. Signup and view all the answers

What happens to DNA methyltransferases during the early stages of embryonic development?

They are suppressed immediately after fertilization. Signup and view all the answers

What is transgenerational inheritance in the context of epigenetics?

Heritable transmission of acquired epigenetic modifications. Signup and view all the answers

What characterizes genetic imprinting?

Only one allele of a gene is transcriptionally active. Signup and view all the answers

What is the role of noncoding RNAs (ncRNAs) or microRNAs (miRNAs) in gene regulation?

They regulate various signaling pathways. Signup and view all the answers

Which statement about CpG dinucleotides is correct?

All methylation occurs at CpG dinucleotides in somatic cells. Signup and view all the answers

What is the process called in which genes are silenced based on parental inheritance?

Imprinting Signup and view all the answers

What typically characterizes an imprinted allele?

Heavy methylation Signup and view all the answers

What syndrome is associated with a deletion on chromosome 15 inherited from the mother?

Angelman syndrome Signup and view all the answers

Which syndrome is characterized by overgrowth and an increased cancer risk?

Beckwith-Wiedemann syndrome Signup and view all the answers

In Russell-Silver syndrome, what is the typical effect on IGF-2?

Downregulation Signup and view all the answers

Which epigenetic modification can be reversed using pharmaceutical intervention?

Methylation changes Signup and view all the answers

How do methylation patterns in twins typically change as they age?

They diverge Signup and view all the answers

In the context of cancer, what happens to methylation densities as tumors progress?

They decline Signup and view all the answers

What effect does fetal alcohol exposure have on the DNA methyltransferases?

Inhibits their activity Signup and view all the answers

What is a common feature of hypermethylation in relation to cancer development?

It is associated with tumor suppressor gene inactivity Signup and view all the answers

Study Notes

Epigenetic Mechanisms

Three major epigenetic mechanisms are under investigation: DNA methylation, histone modifications, and noncoding RNAs (ncRNAs).
DNA methylation involves attachment of a methyl group to cytosine, primarily at CpG dinucleotides.
Histone modifications alter gene expression by adding chemical groups like methyl and acetyl, impacting transcription.
Noncoding RNAs, including microRNAs (miRNAs), regulate diverse signaling pathways; their functions are often not fully understood.
Methylation typically inhibits gene transcription; when heavy methylation occurs, the gene is less likely to be converted to mRNA.
Environmental factors, such as diet and chemical exposure, can induce epigenetic changes.
Transgenerational inheritance refers to passing epigenetic modifications to future generations.

Epigenetics and Human Development

Epigenetic modifications can alter gene expression without changing the DNA sequence.
Housekeeping genes are essential for cell maintenance and typically remain transcriptionally active, escaping epigenetic silencing.
Fertilization results in loss of DNA methylation, with most gene loci becoming unmethylated and transcriptionally active.
DNA methyltransferases reactivation occurs during uterine implantation, establishing cell-lineage-specific marks necessary for organ development.

Genetic Imprinting

Genetic imprinting leads to some genes being transcriptionally active from one parental allele and inactive from the other.
Imprinted alleles usually show heavy methylation, while nonimprinted alleles remain unmethylated.
Prader-Willi syndrome and Angelman syndrome are linked to a deletion on chromosome 15; the disease phenotype depends on the parent's transmission of the deletion.
Beckwith-Wiedemann syndrome involves IGF-2 overexpression causing overgrowth, contrasted by Russell-Silver syndrome, where reduced IGF-2 leads to growth deficiencies.

Inheritance of Epigenetic States

Events during prenatal and early life stages can lead to epigenetic changes associated with phenotypic abnormalities and metabolic syndromes.
Fetal alcohol spectrum disorder may arise from alcohol's repression of DNA methyltransferases during pregnancy.
Fragile X syndrome shows abnormal methylation gain, while facioscapulohumeral muscular dystrophy is characterized by abnormal methylation loss.
Ageing twins exhibit increased differences in DNA methylation patterns, contributing to variances in phenotypes.
Significant lifestyle differences, like smoking, can lead to substantial discrepancies in twins' methylation patterns over time.

Cellular Metabolism

Strong evidence linking epigenetic changes to human disease risk has been observed in cancer studies.
As tumors progress, methylation densities decline, potentially activating oncogenes and facilitating the transition from benign neoplasms to malignancy.
Promoter regions of tumor-suppressor genes often experience hypermethylation, reducing their transcription and tumor inhibition capacity.
Hypermethylation of miRNA genes is also associated with tumorigenesis.
Unlike DNA mutations, epigenetic modifications can potentially be reversed with pharmaceutical treatments; for example, 5-azacytidine is a demethylating agent used in leukemia therapy.

Future Directions

Ongoing research emphasizes the impact of epigenetic states on cell fate determination.
Epigenetic abnormalities play significant roles in carcinogenesis, with implications for developing new therapies aimed at reversing these epigenetic changes in common diseases.

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Description

Explore the key points of Chapter 03 from Huether's 'Understanding Pathophysiology' focusing on epigenetic mechanisms and their implications in disease. This quiz delves into DNA methylation and histone modifications, providing a deeper understanding of these critical biological processes.