Epigenetics and TET Proteins

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Questions and Answers

What role do TET proteins play in epigenetic reprogramming?

TET proteins, specifically TET1, TET2, and TET3, are involved in demethylation and regulate transcriptional activation, tumour suppression, and DNA methylation reprogramming.

Explain the consequences of hypomethylation in genomic stability.

Hypomethylation leads to too little methylation, resulting in increased transcription activity that promotes cell growth and can cause chromosome instability.

What is epigenetic inheritance and how does it differ from genetic inheritance?

Epigenetic inheritance refers to heritable changes in gene expression that do not alter the DNA sequence itself, passed down through epigenetic tags.

Describe the effect of environmental factors on epigenetic control, as seen in bees.

Environmental factors, such as the presence of royal jelly, direct the development of genetically identical larvae into either queen or worker bees by influencing DNA methylation. Signup and view all the answers

What changes in DNA methylation are observed in identical twins as they age?

As identical twins age, their DNA methylation patterns diverge, showing evidence of both hypermethylation and hypomethylation. Signup and view all the answers

What is the role of HAT in gene expression?

HAT, or histone acetyltransferase, adds acetyl groups to lysine residues, leading to transcriptional activation and gene expression. Signup and view all the answers

How does the methylation of cytosine in CpG islands contribute to gene silencing?

Methylation of cytosine residues in CpG islands prevents the binding of transcription factors, leading to condensed chromatin and repression of transcription. Signup and view all the answers

What distinguishes the functions of DNMT1 from DNMT3a and DNMT3b?

DNMT1 is responsible for maintaining established DNA methylation patterns after DNA replication, while DNMT3a and DNMT3b establish new methylation patterns. Signup and view all the answers

Explain the significance of hemimethylated DNA in the context of DNA replication.

Hemimethylated DNA contains one strand methylated and one unmethylated, serving as a template for DNMT1 to add methyl groups to the new strand during DNA replication. Signup and view all the answers

What impact does demethylation have on chromatin structure and transcriptional activity?

Demethylation expands chromatin structure, allowing transcription to occur and enabling gene expression. Signup and view all the answers

Study Notes

Epigenetic Reprogramming

Demethylation is crucial for epigenetic reprogramming, catalyzed by ten-eleven translocation (TET) family of 5mC hydroxylases: TET1, TET2, and TET3.
TET proteins play specific roles:
- TET1 facilitates transcriptional activation and repression.
- TET2 functions in tumor suppression by correcting aberrant methylation.
- TET3 is involved in the DNA methylation reprogramming process.

Hypomethylation and Hypermethylation

Hypomethylation leads to low levels of methylation, resulting in increased transcription and "turning on" genes that stimulate cell growth; this can contribute to chromosomal instability.
Hypermethylation results in excessive methylation, silencing genes that regulate cell growth, repair damaged DNA, and initiate programmed cell death.

Changes of DNA Methylation During Development

Epigenetic inheritance refers to heritable epigenetic tags passed to future generations, altering gene expression without changing the DNA sequence.
Significant epigenetic changes occur at zygote formation, where many parental tags are removed.

Identical Twins and Epigenetic Influence

Comparative genomic hybridization shows that while 3-year-old identical twins exhibit similar DNA methylation patterns, noticeable differences arise by age 50.

Environmental Influence on Epigenetics

Environmental factors can impact development epigenetically, as illustrated by the influence of royal jelly on bee development, affecting the Dnmt3 gene that regulates queen gene expression.

Acetylation and Gene Regulation

Acetylated lysine residues via histone acetyltransferases (HATs) promote transcriptional activation.
Deacetylated lysine residues, processed by histone deacetylases (HDACs), lead to transcriptional repression.

DNA Methylation Basics

DNA methylation, particularly in CpG islands, is vital for epigenetic gene regulation; around 1.5% of human DNA is modified as 5-methylcytosine (5mC).
Methylation at the 5-carbon of cytosine prevents transcription factor binding and leads to condensed chromatin, silencing genes.
Demethylation permits transcription and is essential for normal gene expression during development.

Role of DNA Methyltransferases

Three DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) are crucial for establishing and maintaining DNA methylation patterns.
DNMT1 is responsible for maintaining established patterns, while DNMT3a and DNMT3b help in forming new methylation patterns.
Hemimethylated DNA carries information necessary for determining which strand should be methylated during replication.

Reversible Nature of Methylation

DNA demethylation, the removal of methyl groups, can activate genes depending on specific environmental signals, as seen with queen bee development influenced by royal jelly.

Relevance of Epigenetics

Imprinting disorders can arise from abnormal methylation affecting gene expression in development.
X-inactivation patterns relate to disease expression in X-linked disorders.
Cancer can involve epigenetic silencing of tumor suppressor genes or activation of oncogenes, which may serve as therapeutic targets.
The environment during fetal development influences later disease risk, via epigenetic mechanisms.

DNA Methylation and Cancer

Tumor suppressor genes are often silenced due to hypermethylation, while cancer genomes tend to be hypomethylated, allowing for rapid cell division.
Hyper- and hypomethylation patterns can serve as biomarkers for early detection of certain cancers.

Inherited and Imprinting Disorders

Fragile X syndrome involves silencing due to excessive CGG repeats in the FMR1 gene, leading to intellectual disabilities.
Prader-Willi and Beckwith-Wiedemann syndromes are caused by defects in genomic imprinting and abnormal gene expression due to methylation alterations.

Genomic Imprinting

Imprinting leads to differential expression of genes based on parental origin, influenced by DNA and histone methylation without altering the DNA sequence itself.
Approximately 200 genes in mammals can exhibit this parent-specific expression pattern.

Beckwith-Wiedemann Syndrome

Characterized by embryonic overgrowth and a predisposition to childhood tumors due to genetic and epigenetic alterations on chromosome 11p.
Imbalance in expression from paternal and maternal alleles leads to abnormal growth, linked to IGF2 and CDKN1C genes.

ChIP-seq

A technique that enables identification of DNA sequences bound by specific proteins, facilitating the study of gene regulation.

ENCODE Project

The ENCyclopedia Of DNA Elements (ENCODE) aims to catalog all gene and functional elements in genomes through various assays, including RNA expression and DNA methylation levels.
Data from the project is organized into various annotation levels to enhance understanding of genomic functions.

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Description

Explore the crucial role of TET proteins in epigenetic reprogramming and their function in demethylation. Learn about the different TET family members and their impact on transcriptional regulation and tumor suppression. This quiz will deepen your understanding of DNA methylation processes and the significance of TET enzymes.