20.4 - Epigenetic Control Of Gene Expression

Question 1

What has been the central belief about DNA and heredity since Watson and Crick’s double helix model?

Answer 1

• Since 1953, it has been accepted that DNA contains the instructions for making all parts of an organism.
• However, recent discoveries show that DNA is only part of the heredity story.
• Environmental factors influence gene expression, potentially causing heritable changes in gene function without altering the DNA sequence (a process known as epigenetics).

Question 2

Define epigenetics and its significance in modern science.

Answer 2

• Epigenetics is the study of how environmental factors (e.g., diet, stress, toxins) can cause heritable changes in gene function without altering the DNA sequence.
• It provides insights into diseases like autism and cancer and revisits theories like Lamarckism, which suggested acquired traits could be passed to offspring.

Question 3

What is the epigenome, and how does it function?

Answer 3

• The epigenome is a layer of chemical tags covering DNA and histones. These tags determine the shape of the DNA-histone complex, influencing gene activity.
  —>Tightly packed DNA-histone complexes result in epigenetic silencing, keeping genes inactive.
  —> Unwrapped complexes expose DNA, allowing active transcription.
• The epigenome is flexible and responds to environmental changes, switching genes on or off as needed.

Question 4

How does the environment shape the epigenome?

Answer 4

• The epigenome adapts to environmental signals, such as diet and stress, adjusting the wrapping and unwrapping of DNA around histones to activate or silence genes.
• This dynamic response acts as a cellular memory, influenced by factors from early fetal development (e.g., maternal nutrition) to external environmental signals throughout life.

Question 5

What mechanisms are involved in epigenetic regulation within cells?

Answer 5

• Environmental signals initiate a cascade of intracellular communication, culminating in a specific protein interacting with DNA to regulate gene activity via:
  1) Acetylation of histones - Activates or inhibits genes by altering histone structure.
  2) DNA methylation - Adds or removes methyl groups, attracting enzymes to further regulate gene expression.

Question 6

What role does early development play in shaping the epigenome?

Answer 6

• In early development, signals from fetal cells and maternal nutrition critically shape the epigenome.
• This period establishes cellular memory, setting the foundation for how environmental factors will influence gene activity throughout the organism’s life.

Question 7

Why is epigenetics important in understanding and treating diseases?

Answer 7

• Epigenetics explains how environmental factors can cause diseases like autism and cancer by altering gene expression without changing the DNA sequence.
• This understanding opens pathways for potential treatments targeting the epigenome.

Question 8

How does the flexibility of the epigenome differ from the fixed nature of the DNA code?

Answer 8

• While the DNA code is unchanging, the epigenome is adaptable, responding dynamically to environmental stimuli.
• This flexibility allows genes to be switched on or off in response to changes, providing a mechanism for environmental influence on heredity.

Question 9

How does the association between histones and DNA affect gene expression?

Answer 9

• Weak association: DNA-histone complex is less condensed, allowing transcription factors to access DNA and initiate mRNA production (gene is switched on).
• Strong association: DNA-histone complex is tightly packed, preventing transcription factors from accessing DNA (gene is switched off).
  ——> Condensation inhibits transcription.

Question 10

What processes can cause condensation of the DNA-histone complex, inhibiting transcription?

Answer 10

1) Decreased acetylation of histones.
2) Increased methylation of DNA.
—> Both processes make DNA less accessible to transcription factors, turning genes off.

Question 11

What is acetylation, and how does it affect gene expression?

Answer 11

• Acetylation: Transfer of an acetyl group (from acetyl coenzyme A) to histones, reducing their positive charge and weakening their attraction to the negatively charged DNA. This loosens the DNA-histone complex, allowing transcription factors to access DNA (gene switched on).
• Deacetylation: Removal of an acetyl group, increasing positive charges on histones, strengthening DNA-histone binding, and preventing transcription (gene switched off).

Question 12

How does decreased acetylation affect the DNA-histone complex and gene expression?

Answer 12

• Decreased acetylation increases positive charges on histones, strengthening their attraction to DNA’s phosphate groups.
• This tightens the DNA-histone complex, making DNA inaccessible to transcription factors and turning the gene off.

Question 13

What is methylation, and how does it regulate gene expression?

Answer 13

• Methylation is the addition of a methyl group (CH₃) to cytosine bases of DNA. It inhibits transcription by:
  1) Preventing transcription factors from binding to DNA.
  2) Attracting proteins that condense the DNA-histone complex by inducing histone deacetylation.

Question 14

What role do transcription factors play in gene expression, and how can their access be inhibited?

Answer 14

• Transcription factors bind to DNA to initiate mRNA production. Access is inhibited by:
  1) Condensed DNA-histone complexes caused by decreased acetylation.
  2) Methylation of DNA, which either blocks transcription factor binding or promotes deacetylation-induced condensation.

Question 15

What two primary modifications inhibit transcription and switch genes off?

Answer 15

• Decreased acetylation of histones: Strengthens DNA-histone binding, condensing the complex.
• Increased methylation of DNA: Blocks transcription factor binding. Attracts proteins causing DNA-histone condensation via deacetylation

Question 16

What molecule donates acetyl groups in histone acetylation, and what reaction reverses this process?

Answer 16

• Acetyl donor: Acetyl coenzyme A (from the link reaction in respiration).
• Reversal: Deacetylation, which removes acetyl groups, strengthens histone-DNA binding, and inhibits transcription.

Question 17

How does gestational diabetes in mothers illustrate epigenetic inheritance?

Answer 17

• In gestational diabetes, the fetus is exposed to high glucose concentrations, causing epigenetic changes in the daughter’s DNA.
• These changes increase the likelihood that the daughter will develop gestational diabetes in the future.

Question 18

How are epigenetic tags typically reset in sperm and eggs?

Answer 18

• During early development, a specialized cellular mechanism erases most epigenetic tags, returning cells to a genetic “clean slate.”
• However, some tags escape erasure and can pass unchanged to offspring.

Question 19

How can epigenetic changes contribute to disease?

Answer 19

• Abnormal activation or silencing of genes caused by epigenetic changes can lead to diseases like cancer.
• For example, activation of inactive genes or silencing of active genes may trigger cancer.

Question 20

What did researchers discover about DNA methylation in colorectal cancer patients in 1983?

Answer 20

• Diseased tissues had less DNA methylation compared to normal tissues.
• Reduced methylation increases gene activity, switching on more genes than normal, which can contribute to cancer development.

Question 21

What happens to promoter region methylation in cancer cells?

Answer 21

• In cancer cells, specific promoter regions that are normally unmethylated become highly methylated.
• This abnormal methylation silences genes that should be active, contributing to early cancer development.

Question 22

How can epigenetic changes increase the risk of mutations?

Answer 22

• Some active genes repair DNA to prevent cancers.
• Increased methylation of these protective genes switches them off, leaving DNA damage unrepaired and increasing the risk of mutations that lead to cancer.

Question 23

What is the goal of epigenetic therapy, and how does it work?

Answer 23

• Epigenetic therapy aims to counteract harmful epigenetic changes by using drugs that target histone acetylation or DNA methylation.
• For example, drugs that inhibit DNA methylation enzymes can reactivate silenced genes.
• Therapy must specifically target cancer cells to avoid activating harmful gene transcription in normal cells.

Question 24

How is epigenetics used in disease diagnostics?

Answer 24

• Diagnostic tests have been developed to detect early-stage diseases (e.g., cancer, brain disorders, arthritis) by measuring levels of DNA methylation and histone acetylation.
• Early detection allows for timely treatment, improving chances of a cure.

Question 25

What is a critical risk of epigenetic therapy, and how is it managed?

Answer 25

• If epigenetic drugs affect normal cells, they could activate harmful gene transcription and induce cancer.
• To prevent this, therapy is carefully targeted to affect only cancer cells.

Question 26

What is the role of RNA interference in gene expression?

Answer 26

RNA interference inhibits the translation of mRNA into a polypeptide by breaking mRNA down before its information can be translated. This prevents the expression of the gene.

Question 27

What is siRNA, and how is it involved in RNA interference?

Answer 27

• Small interfering RNA (siRNA) is a type of small RNA molecule that guides the RNA interference mechanism.
• It pairs with complementary bases on mRNA, enabling an enzyme to cut the mRNA into smaller sections, blocking gene expression.

Question 28

Describe the mechanism for how siRNA works

Answer 28

1) An enzyme cuts large double-stranded molecules of RNA into smaller sections called small interfering RNA (siRNA)
2) One of the two siRNA strands combines with an enzyme
3) The siRNA molecule guides the enzyme to a messenger RNA molecule by pairing up its bases with the complementary ones on a section of the mRNA molecule
4) Once in position, the enzyme cuts the MRNA into smaller sections
5) The mRNA is no longer capable of being translated into a polypeptide.
6) This means that the gene has not been expressed, that is, it has been blocked