Epigenetic Control of Gene Expression - 20.4

Question 1

What is meant by the terms epigenetics?

Answer 1

Environmental factors can cause heritable changes in gene function without changing the base sequence of DNA.

Question 2

How can epigenetics be applied to scientific research?

Answer 2

Epigenetics provides explanations as to how environmental factors such as diet, stress, toxins, etc. can subtly alter the genetic inheritance of an organism’s offspring. It is helping to explain, and maybe cure, illnesses ranging from autism to cancer.

Question 3

What is histones?

Answer 3

Proteins that DNA is wrapped around.

Question 4

What is the epigenome?

Answer 4

DNA and histones are covered in chemicals, sometimes called tags. These chemical tags form a second layer known as the epigenome.

Question 5

What does the epigenome determine?

Answer 5

The shape of the DNA-histone complex.

Question 6

Is the epigenome fixed or flexible and why?

Answer 6

Flexible because its chemical tags response to environmental changes. Factors like diet and stress can cause the chemical tags to adjust the wrapping and unwrapping of DNA and so switch genes on and off.

Question 7

What is the epigenome of a cell?

Answer 7

The accumulation of the signals a cell has received during its lifetime.

Question 8

Where do the signals come from in early development?

Answer 8

In early development, the signals come from within the cells of the fetus and the nutrition provided by the mother is important in shaping the epigenome at this stage.

Question 9

Where do the signals come from after birth?

Answer 9

After birth, and throughout life, environmental factors affect the epigenome, although signals from within the body, for example, hormones, also influence it. these factors cause the epigenome to activate or inhibit specific sets of genes.

Question 10

What effect does the environmental signal have?

Answer 10

The environmental signal stimulates proteins to carry its message inside the cell from where it is passed by a series of other proteins into the nucleus. Here the message passes to a specific protein which can be attached to a specific sequence of bases on the DNA.

Question 11

What happens once the protein has attached to the bases on DNA?

Answer 11

Once attached the protein has two possible effects. It can change:

• Acetylation of histones leading to the activation or inhibition of a gene.
• Methylation of DNA by attracting enzymes that can add or remove methyl group.

Question 12

What happens where the association of histones with DNA is weak?

Answer 12

The DNA-histone complex is less condensed (loosely packed). In this condition the DNA is accessible by transcription factors, which can initiate production of mRNA, that is, can switch on a gene.

Question 13

What happens where the association of histones with DNA is stronger?

Answer 13

The DNA-histone complex is more condensed (tightly packed). In this condition the DNA is not accessible by transcription factors, which therefore cannot initiate production of mRNA, that is, the gene is switched off.

Question 14

What does the condensation of the DNA-histone complex cause and how?

Answer 14

Condensation of the DNA-histone complex therefore inhibits transcription. It can be brought about by decreased acetylation of histones or by methylation of DNA.

Question 15

What is acetylation?

Answer 15

Acetylation is the process whereby an acetylene group is transferred to a molecule.

Question 16

Where is the acetyl group donated from in the decreased acetylation of associated histones?

Answer 16

Acetylcoenzyme A

Question 17

What is deacetylation?

Answer 17

The reverse reaction of acetylation, where an acetyl group id removed from a molecule.

Question 18

What affect does decreased acetylation have?

Answer 18

Decreased acetylation increases the positive charge on histones and therefore increases their attraction to the phosphate groups of DNA. The association between DNA and histones is stronger and the DNA is not accessible to transcription factors. These transcription factors cannot initiate mRNA production from DNA, so the gene is switched off.

Question 19

what is methylation?

Answer 19

The addition of a methyl group (CH3) to a molecule.

Question 20

Where is the methyl group added in increased methylation of DNA?

Answer 20

In this case the methyl group is added to the cytosine bases of DNA.

Question 21

How does methylation inhibit the transcription of genes?

Answer 21

Methylation normally inhibits the transcription of genes in two ways:

• Preventing the binding of transcriptional factors of DNA.
• Attaching protein that condense the DNA-histone complex (by inducing deacetylation of the histones) making the DNA inaccessible to transcription factors.

Question 22

What was shown from the experiments in to epigenetics?

Answer 22

• Good maternal behaviour in rats transmits epigenetic information onto their offspring’s DNA without passing through an egg or sperm.
• In humans, when a mother has gestational diabetes, the foetus is exposed to high concentrations of glucose. These high glucose concentrations cause epigenetics in the the daughter’s DNA, increasing the likelihood that she will develop gestational diabetes herself.

Question 23

What happens to the egg and sperm cells during the earliest stages of development?

Answer 23

A specialised cellular mechanism searches the genome and erases it epigenetic tags in order for it to return the cells to a genetic ‘clean slate’. However, a few epigenetic tags escape this process and pass unchanged from parent to offspring.

Question 24

How can epigenetics cause disease?

Answer 24

Altering any of the epigenetic processes can cause abnormal activation or silencing of genes. Some alterations have been associated with a number of diseases including cancer. In some cases the activation of a normally inactive gene can cause cancer, in other cases it is the inactivation of a normally active gene that gives rise to the disease.

Question 25

What did researcher find out about colorectal cancer in 1983 and what does this show?

Answer 25

Researched found that diseased tissue taken from patients with colorectal cancer had less DNA methylation than normal tissue from the same patients. As increased methylation normally inhibits transcription, these patients with less DNA methylation would have higher than normal gene activity - more genes were turned on.

Question 26

What happens near promoter regions of DNA?

Answer 26

Specific regions of DNA (ones near regions called promoter regions) have no methylation in normal cells. In cancer cells, however, these regions become highly methylated causing genes that should be active switch off. This abnormality happens early in the development of cancer.

Question 27

How can epigenetic changes increase the incidence of mutations?

Answer 27

Some active genes normally help repair DNA and so prevent cancers. In people with various types of inherited cancer, it is found that increased methylation of these genes has led to these protective genes being switched off, leading to damaged base sequences in DNA not being repaired and so can lead to cancer.

Question 28

How can epigenetic therapy be used to treat diseases?

Answer 28

Drugs can be used to inhibit certain enzymes involved in either histone acetylation or DNA methylation. For example, drugs that inhibit enzymes that cause DNA methylation can reactivate genes that have been silence.

Question 29

Why must epigenetic therapy be so specifically targeted?

Answer 29

Epigenetic therapy must be specifically targeted on cancer cells. If the drugs were to affect normal cells they could activate gene transcription and make them cancerous, so causing the very disorder they were designed to cure.

Question 30

How can epigenetics be used to aid in diagnostic tests?

Answer 30

They can help to diagnose the early stages of diseases such as cancer, brain disorders and arthritis. These tests can identify the level of DNA methylation and histone acetylation at an early stage of disease. This allows those with these diseases to seek early treatment and so have better changes of cure.

Question 31

How can the translation of mRNA be inhibited?

Answer 31

The translation of mRNA produced by a gene can be inhibited by breaking mRNA down before its coded information can be translated into a polypeptide.

Question 32

What is an example of a molecule that may be used in inhibition of translation?

Answer 32

Small interfering RNA (siRNA)

Question 33

How does siRNA work to inhibit translation?

Answer 33

• An enzyme cuts large double-stranded molecules of RNA into smaller sections called small interfering RNA.
• One of the two siRNA strands combine with an enzyme.
• 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.
• Once in position, the enzyme cuts the mRNA into smaller sections.
• The mRNA is no longer capable of being translated into a polypeptide.
• This means that the gene has not been expressed, that is, it has been blocked.

Question 34

What is Prada-Willi syndrome?

Answer 34

A genetic disease that is a result of seven genes on chromosome 15 being deleted. This is thought to be involved with epigenetic inheritance.