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20 Cards in this Set

  • Front
  • Back

Gene expression isn’t just controlled by transcription factors and RNAi.


Epigenetic control can determine whether a gene is expressed or not.


Describe simply what epigenetic control involves?

• attachment or removal of chemical groups (epigenetic marks) to DNA or histone proteins


• The base sequence of DNA is NOT altered


• the epigenetic marks alter how easy it is for enzymes and other proteins needed for transcription to transcribe the DNA

How do we end up with epigenetic changes to gene expression (why do epigenetic marks develop on some genes and not others)?

• epigenetic changes to gene expression play many roles in normal cell processes - so the changes happen and vary all the time


• can occur in response to changes in the environment e.g. pollution, lack of food

Are epigenetic marks inherited?

• some are, but they have to escape the removal process to be passed on to the offspring


• most epigenetic marks on the DNA are removed between generations

How is it that the expression of some genes in an offspring can be affected by environmental changes that affected their parents (or even grandparents)?

• some epigenetic marks escape the removal process and are passed on to the offspring


e.g. if your grandad developed epigenetic marks on certain genes due to a lack of food, you could have these epigenetic marks on your DNA too

Why are most epigenetic marks removed between generations?

Cells from the fertilised egg need to be able to become any type of cell (need to be totipotent)


• having epigenetic marks would just make the early cells more specialised


(Epigenetic marks are important in cell specialisation)

Developing epigenetic marks is referred to as ‘having epigenetic changes’

-

There are loads of epigenetic mechanisms.


What epigenetic mechanisms (used to control gene expression) do you need to know about?

• methylation of DNA


• acetylation of histones

What is Methylation of DNA?


How does it occur?

A Methyl group (an epigenetic mark) is attached to the DNA of a gene by ‘DNA methyltransferases’ (enzymes)


The Methyl group attaches at a CpG site (where a cytosine and guanine base are next to eachother in the DNA)

How can Methylation of DNA lead to genes not being expressed?

Increased Methylation


• changes the DNA structure so that the transcriptional machinery (enzymes etc.) can’t interact and transcribe the gene

What is Acetylation of histones?

Addition (or removal) of Acetyl groups (-COCH3) onto histones in Chromatin

Remember:


• histones are proteins that DNA wraps around to form Chromatin


• Chromatin makes up chromosomes

-

Describe how different amounts of acetylation of histones affects the control of gene expression?

• The more histones are acetylated, the less condensed the Chromatin is - this means the transcriptional machinery can access the DNA - genes can be transcribed


• less acetylation, Chromatin more condensed, genes can’t be transcribed as the transcriptional machinery can’t physically access them

Which enzymes are responsible for removing acetyl groups from histones?

Histone deacetylase (HDAC) enzymes

Mutations can occur in tumour-suppressor genes and proto-oncogenes that cause cancer.


Epigenetics can also make these genes more likely to cause tumours. Describe how?

Hypermethylation of TS genes, the genes are not transcribed, TS proteins not made (to slow cell division), cells able to divide uncontrollably by mitosis, tumours develop


Hypomethylation of proto-oncogenes, act as oncogenes, increased production of the proteins that encourage cell division, cells stimulated to divide uncontrollably, tumours develop

Epigenetics can play a role in the development of disease (e.g. abnormal methylation causing cancer).


Here is an example of how epigenetics plays a role in the development of another disease:


(Don’t need to learn)

Angelman syndrome


• a genetic disorder


• causes by a deletion mutation of a region of chromosome 15


• the maternal allele in this affected region is missing - so a protein is not produced by this allele


• the paternal allele is present, but it is unable to compensate because it is switched off by hypermethylation, and therefore the gene is not transcribed


• a protein is not produced - leads to symptoms of the disorder

Why are Epigenetic changes a lot easier to treat than DNA sequence mutations?

Epigenetic changes are reversible

Drugs are constantly being designed to treat some genetic conditions by counteracting the epigenetic changes that cause the disease.


How might a drug stop increased methylation of TS genes causing cancer?

• drugs inhibit the DNA methyltransferases (enzymes) that attach the methyl groups

Drugs are constantly being designed to treat some genetic conditions by counteracting the epigenetic changes that cause the disease.


How might a drug stop increased methylation of TS genes causing cancer?

• drugs inhibit the DNA methyltransferases (enzymes) that attach the methyl groups


• so that the TS genes aren’t switched off

Some diseases are caused by decreased acetylation of histones.


How can drugs stop this?

• Histone deacetylase (HDAC) inhibitors


• inhibit it’s activity, acetyl groups are not removed


• the genes can be transcribed

What are the dangers of creating drugs to treat disease by counteracting epigenetic changes?

• epigenetic changes take place normally in all cells, so it’s important that the drugs are specific


- if these drugs counteract epigenetic changes in normal cells, transcription may be activated when it normally wouldn’t be, some genes could become overactive (expressed more than they should be)


e.g. if this happens to proto-oncogenes the normal cells could become cancerous