Epigenetics and Post-Translational Modifications

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Questions and Answers

What is a primary function of epigenetic regulation?

Creating additional DNA copies

Increasing the number of genes in the genome

Altering the primary DNA sequence

Promoting immediate organism-level adaptation to the environment (correct)

Which of the following is NOT considered a major epigenetic regulator?

CpG DNA methylation

Protein phosphorylation (correct)

Histone modifications

Noncoding RNA expression

What type of modifications are post-translational modifications (PTMs) primarily involved in?

Alterations in DNA structure

Changes to nucleic acid sequences

Chemical modifications of proteins (correct)

Replication of genetic material

What is the primary role of DNA methylation in gene regulation?

Inhibits transcription factor binding to promoters Signup and view all the answers

How does alternative splicing contribute to the diversity of proteins?

Through the creation of multiple mRNA transcripts from a single gene Signup and view all the answers

Which of the following best describes the function of post-translational modifications?

To regulate the activity and interactions of proteins Signup and view all the answers

How does histone acetylation generally affect gene expression?

It promotes transcription by making DNA more accessible Signup and view all the answers

Which of the following statements about microRNAs is true?

They control target gene expression post-transcriptionally Signup and view all the answers

What is a consequence of the presence of more than a million proteins derived from the human genome?

It shows that single genes can encode multiple proteins Signup and view all the answers

What occurs immediately after DNA replication regarding methylation?

One strand is methylated and the other is unmethylated Signup and view all the answers

Which process is NOT involved in increasing proteome complexity?

Activator protein binding to RNA Signup and view all the answers

What is the effect of histone methylation on transcription?

It can either activate or silence gene expression Signup and view all the answers

Which of the following post-translational modifications can impact protein localization?

Methylation Signup and view all the answers

Which enzyme is responsible for adding methyl groups to DNA?

Maintenance methyltransferase Signup and view all the answers

Which modification generally leads to increased gene accessibility in chromatin?

Histone acetylation Signup and view all the answers

What does chromatin remodeling refer to?

Changes in histone and DNA structure affecting gene expression Signup and view all the answers

What is the role of methionine aminopeptidase (MAP) in N-terminal acetylation?

To cleave the N-terminal methionine Signup and view all the answers

What type of acetylation occurs on polypeptide chains during translation?

Co-translational acetylation Signup and view all the answers

What is the primary reason for histone acetylation being significant in gene regulation?

It influences the interaction between DNA and transcription factors Signup and view all the answers

Which enzymes are responsible for adding acetyl groups to histones?

Histone acetylases (HATs) Signup and view all the answers

How does a single lysine alteration on histones affect the cell?

It alters cellular metabolism or transcription Signup and view all the answers

What role do miRNAs play in gene expression?

They target and degrade complementary mRNAs Signup and view all the answers

What determines the fate of a target mRNA when bound by RISC?

The extent of complementarity to the bound miRNA Signup and view all the answers

What effect do environmental chemicals have on miRNAs?

They can alter miRNA stability and function Signup and view all the answers

What is the primary effect of transcription factors activated by environmental contaminants on DNA methylation?

They inhibit DNA methyltransferase activity at specific sites. Signup and view all the answers

How does lack of transcription factor binding affect DNA methylation?

It allows DNA methyltransferase access, leading to hypermethylation. Signup and view all the answers

What type of air pollutants are associated with changes in DNA methylation levels?

Particulate matter, ozone, and other chemicals. Signup and view all the answers

Which gene is specifically mentioned as being influenced by traffic-related air pollution?

TET1. Signup and view all the answers

What is a consequence of prenatal exposure to air pollution on DNA methylation?

It alters gene-specific methylation patterns depending on exposure timing. Signup and view all the answers

How does arsenic exposure affect DNA methylation?

It can result in both hypomethylation and hypermethylation. Signup and view all the answers

What is the suggested relationship between prenatal window alterations in DNA methylation and later-life disease?

Alterations during this period can lead to predisposition to disease later in life. Signup and view all the answers

Which of the following is NOT an environmental factor leading to changes in DNA methylation?

Genetic mutations. Signup and view all the answers

What is the primary effect of arsenic exposure on DNA methylation in males, as indicated by recent research?

Induction of hypermethylation Signup and view all the answers

Which health outcomes have been associated with specific genes affected by arsenic exposure?

Lower birth weight and diabetes Signup and view all the answers

What change in DNA methylation does BPA primarily induce in women and young girls?

Hypomethylation Signup and view all the answers

Which of the following is NOT a gene affected by BPA exposure according to the research?

Contactin-associated protein-like 2 (CNTNAP2) Signup and view all the answers

What effect does tobacco smoke exposure have on DNA methylation patterns?

Induces genetic instability and global hypomethylation Signup and view all the answers

In relation to nutritional factors, what impact can early-life nutrition have?

Affects developmental programming and later-life health Signup and view all the answers

Which gene is commonly affected by prenatal tobacco smoke exposure?

Myosin IG (MYO1G) Signup and view all the answers

What is the primary public health concern associated with BPA?

Its widespread exposure and unclear health effects Signup and view all the answers

Which nutrient is essential for fetal development and linked to global methylation measures?

Folate Signup and view all the answers

How does paternal intake of methyl donor nutrients influence offspring?

It affects growth and metabolism. Signup and view all the answers

What is one of the major gaps in epigenetics research regarding nutritional assessment?

Assessment of environmental mixtures. Signup and view all the answers

Why is it important to study tissue-specific changes in methylation marks?

To understand changes specific to disease biomarkers. Signup and view all the answers

What nutrient deficiency may lead to hypomethylation?

Folate Signup and view all the answers

Which aspect of methylation research has received limited attention and requires longitudinal studies?

Functional consequences and stability over time. Signup and view all the answers

What role do micronutrients like the vitamin B family play in methylation?

They are critical for maintaining methylation status. Signup and view all the answers

What is a significant result of environmental influences on the epigenome?

It may inform strategies for disease prevention and personalized medicine. Signup and view all the answers

Study Notes

Environmental Influences on the Epigenome

Epigenetics studies heritable gene changes not due to DNA sequence alterations
Epigenetic machinery influences gene expression by affecting mRNA and protein levels
Epigenetic regulation enables organism-level adaptation to the environment
Three major epigenetic regulators are: histone modifications, DNA methylation, and non-coding RNA expression

Post-Translation Modifications

Post-translational modifications (PTMs) add variations to proteins in the proteome—proteins made from genes, changing how much protein there is.
Examples of PTMs: methylation, acetylation, phosphorylation, glycosylation
PTMs can affect protein folding, stability, localization, function, activation, and interactions

Diversity and Complexity of Proteins

Post-translational modifications (PTMs) are chemical changes that modify protein function
PTMs affect activity, localization, and interactions with other molecules like proteins, nucleic acids, lipids, and cofactors

PTMs Increase Proteome Diversity

Human genome (21,000-22,000 genes), and human proteome comprises over 1 million proteins
Single genes may encode multiple proteins through genomic recombination, alternative promoters, differential transcription termination, and alternative splicing.
PTMs further extend proteome complexity from the genomic level

Epigenetics

Changes to gene function that are not due to DNA alterations
Heritable changes caused by transcriptomic and post-transcriptional regulators

Epigenetic Mechanisms

DNA methylation – adding methyl groups to cytosines in DNA; often inhibiting transcription factors from binding to DNA
Chromatin remodeling (histone methylation, acetylation/deacetylation) altering the structure of chromatin, affecting the accessibility of DNA to transcription factors.
MicroRNAs (small non-coding RNAs) influencing gene expression post-transcriptionally

1-DNA Methylation

Methylation is the addition of a methyl group to a cytosine nucleotide.
The methyl group is added to the cytosine.
After replication, maintains the methylation pattern

2-Chromatin Remodeling- Histone Methylation

Histone methylation and demethylation influence the accessibility of DNA for transcription.
Methyl groups attached to amino acid residues on histones affect chromatin structure.
Modifying histones influences gene regulation.

Acetylation

Chemical modification transferring an acetyl group to a nitrogen in protein, a reversible process in eukaryotic proteins.
N-terminal acetylation, a co-translational process, attaching an acetyl group to the N-terminus of a polypeptide chain (while still binding to ribosomes), has unclear biological significance.

3- Chromatin Remodeling-Histone Acetylation

Acetylation of lysine residues on histone N-terminals, regulating gene expression.
Acetylation (adding acetyl groups) and deacetylation (removing acetyl groups) of histones by HATs and HDACs.
Histone acetylation and deacetylation have a well-established link to aging and various neurological and cardiovascular diseases

MicroRNAs

Small non-coding RNAs that influence gene expression
miRNAs form double-stranded precursor molecules in the nucleus.
miRNAs are processed to a mature, single-stranded miRNA.
miRNAs associate with proteins in a complex (RISC).
This RISC complex searches for complementary sequences on mRNA transcripts;
mRNA is either targeted for degradation or translation suppression

miRNAs and Environment

miRNAs are essential epigenetic regulators, impacting gene and protein expression.
These miRNAs play a key role in development, are sensitive to environmental chemicals, and are involved in pregnancy-related diseases.

Environmental Factors Influencing DNA Methylation

Environmental exposures (e.g., air pollution, metals, toxins), specific contaminants, nutritional factors, and lifestyle factors influence methylation patterns.
These factors can impact both global and gene-specific methylation.

Gene-Specific Methylation

Site-specific methylation is measured in addition to global methylation.
This provides insight into disease development.
Studies show that exposing mice to environmental contaminants and/or specific nutrition influences gene methylation that correlates with adult health and disease, including patterns in prenatal development.

Gene-Specific Methylation in Humans

Studies show that alterations in methylation at a single gene locus can influence disease susceptibility and future health outcomes.
Studies using Dutch Hunger Winter data demonstrate how famine exposures can lead to variations in prenatal methylation patterns affecting later-life health.
A single alteration in methylation could impact susceptibility to disease in adults.

Transcription Factors Triggered by Environmental Exposure Influence Site-Specific Methylation

Environmental contaminants can trigger activation, or repression, of transcription factors as a cellular defense response.
Specific transcription factors can influence methylation patterns at particular sites in the genome by impacting the activation/inhibition of methyltransferases (DNMTs), resulting in either hypermethylation or hypomethylation.

Environmental Factors Causing Changes in DNA Methylation

A wide variety of factors like air pollution, toxic metals, and specific chemicals can induce changes to DNA methylation. Exposures to different substances may affect DNA differently in men than women, and at certain life stages, like prenatal development

Nutritional Factors

Nutritional factors (e.g., folate, methionine, betaine, choline) can modify global methylation levels.
Paternal intake of these factors influence global methylation, impacting later-life health, specifically in young offspring.
Diet and nutrient intake impact gene methylation status; specific genes and outcomes like obesity and various diseases have been associated with changes in methylation influenced by nutritional statuses and patterns in intake.

Future Directions in Epigenetics Research

Further research is needed on the joint impacts of multiple environmental factors on methylation
Research should include sex-specific effects and tissue-specific methylation patterns to tailor more precise assessments and interventions.
Evaluating the long-term stability of methylation changes and its effect on gene expression is crucial.

Conclusion

There's a strong link between environmental influences, particularly nutritional factors and those specific chemical exposures, through exposure-associated DNA methylation.
Understanding epigenetic principles is important for developing preventive health strategies.

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Description

This quiz explores the crucial aspects of epigenetics, including how environmental factors influence the epigenome, and the role of post-translational modifications in protein function. Test your knowledge on histone modifications, DNA methylation, and various PTMs such as methylation and phosphorylation. Gain a deeper understanding of how these processes contribute to the diversity and complexity of proteins.