Factors affecting gene expression

In a nutshell

Transcription factors are proteins that affect gene expression, they encourage or prevent certain genes from being transcribed by binding DNA. Other molecules such as RNA interference molecules are able to inhibit translation. Epigenetics also affects gene expression, with certain epigenetic markers preventing or inhibiting it.

Transcription factors

Definition

Transcription factors are proteins that control gene transcription.

All cells in an organism carry the same genes, however, not all of these genes are expressed. This leads to the production of different proteins that determine the cell's shape and function. It is this ability that allow cells to differentiate into different types. This differential expression is controlled by transcription factors.

Biology; Modern genetics; KS5 Year 12; Factors affecting gene expression — 1. Transcription factors, 2. Start of gene, 3. Activator, 4. RNA polymerase, 5. Repressor, 6. RNA polymerase is blocked from binding, 7. Nucleus, 8. Cytoplasm

1.	Transcription factors travel from the cytoplasm to the nucleus.
2.	When in the nucleus, they bind to specific DNA sequences that are near their target gene.
3.	Transcription factors called activators increase the rate of transcription. They can do this by helping RNA polymerase to bind to the target and start transcription.
4.	Transcription factors called repressors do the opposite. They decrease the rate of transcription and they can do this by preventing RNA polymerase from binding to the target.

Oestrogen

Oestrogen is a steroid hormone that is heavily involved in the menstrual cycle. It has the ability to affect gene expression by binding a transcription factor.

Biology; Modern genetics; KS5 Year 12; Factors affecting gene expression

1.	Oestrogen can diffuse across the cell surface membrane as it is soluble in lipids.
2.	Oestrogen binds to a transcription factor known as an oestrogen receptor. This forms a oestrogen-oestrogen receptor complex.
3.	The binding of oestrogen causes the transcription factor to change shape.
4.	The oestrogen-oestrogen receptor complex travels from the cytoplasm into the nucleus where it binds specific DNA sequences near its target gene. The oestrogen-oestrogen receptor complex can act as an activator of transcription, or a repressor. It depends on the type of cell and the target gene.

RNAi

In eukaryotic cells, the expression of genes is also affected by RNA interference (RNAi). This is when small, double-stranded RNA molecules are able to the stop the translation of mRNA. There are two types of RNA molecules involved and these are called small interfering RNA (siRNA) and microRNA (miRNA).

siRNA

Biology; Modern genetics; KS5 Year 12; Factors affecting gene expression

1.	Nucleus.
2.	RNA polymerase.
3.	mRNA.
4.	Transcribed mRNA exits the nucleus and enters the cytoplasm.
5.	In the cytoplasm (6.), siRNA unwinds as it becomes associated with different proteins. Single-stranded siRNA then binds to the mRNA as it has a complementary base sequence.
7.	The proteins that are associated with the siRNA cut the mRNA into small fragments so it can no longer be translated.
8.	The mRNA fragments are then degraded.

Note: In plants, a similar process occurs with miRNA.

miRNA in mammals

Biology; Modern genetics; KS5 Year 12; Factors affecting gene expression

1.	Nucleus.
2.	RNA polymerase.
3.	mRNA.
4.	Transcribed mRNA exits the nucleus and enters the cytoplasm (5.).
6.	Unlike siRNA, miRNA isn't fully complementary to the mRNA. It is therefore less specific and can target many mRNA molecules. miRNA associates with proteins that allow it to bind to the mRNA in the cytoplasm. The miRNA-protein complex blocks the translation of the mRNA.
7/8.	The mRNA is then either stored or degraded. This means it may be translated at another time.

The lac repressor

The bacterium Escherichia coli, uses glucose in respiration. However, if glucose isn't available, it can use lactose.

1.	In the presence of lactose, E. coli produces an enzyme called $\beta$ -galactosidase that can digest it. Note: This enzyme is only expressed in the presence of lactose.
2.	A transcription factor called the lac repressor controls the production of this enzyme
3.	If there is no lactose, the lac repressor binds to DNA at the start of the $\beta$ -galactosidase gene. This prevents transcription.
4.	If there is lactose, it will bind to the lac repressor. The lac repressor will no longer be able to bind to DNA and inhibit transcription.

Epigenetics

Epigenetics involves heritable changes in gene function but no changes to the actual base sequence of DNA. In eukaryotes, epigenetics determines whether genes are transcribed and translated through the attachment or removal of chemical groups. These chemical groups are called epigenetic markers.

Epigenetic markers do not change the DNA sequence, instead they make it more or less easy for certain enzymes and proteins, that are essential for transcription, to interact with the DNA. Epigenetic markers are a result of environmental factors such as pollution.

Methylation

One type of epigenetic marker, is a methyl group ( $-CH_3$ ). Methyl groups attach to CpG islands on genes. These are sections of DNA with repeated cytosine and guanine bases that are linked with a phosphodiester bond.

Increased methylation causes changes to the DNA structure, these changes prevent transcriptional machinery from interacting with the gene. This means the gene will not be expressed.

Acetylation

Another type of epigenetic marker is an acetyl group. Acetyl groups bind to histones and histones are proteins that DNA molecules wrap around to form chromatin. Chromatin can be highly condensed or much less condensed.

When histones become acetylated, chromatin becomes less condensed. This means transcriptional machinery has easy access to DNA and it can be readily transcribed.

However, when acetyl groups are removed from histones, by histone deacetylase enzymes, the chromatin becomes highly condensed. This prevents transcription as the transcriptional machinery cannot access the DNA.

Biology; Modern genetics; KS5 Year 12; Factors affecting gene expression — A. Chromatin is less condensed, 1. Histone, 2. DNA, 3. Acetyl group. B. Chromatin is more condensed, 1. Histone, 2. DNA.

Drugs

As epigenetic changes are reversible, they can be targets for drugs. These drugs are designed to overcome the epigenetic changes that have caused a disease.

Examples

Azacitidine is used to treat cancers that are caused by increased by methylation of tumour suppressor genes.
Romidepsin is used to treat cancers that are caused by increased acetylation of certain genes.