topic 8 - the control of gene expression

What is control of gene expression?

The control over transcription and translation in protein synthesis which effects whether the protein coded by a gene is converted made and in what quantities.

What is transcription controlled by?

Transcription factors - proteins that are able to bind to specific DNA sequences (as their 3D structure is complementary).

Transcription factors tend to work on specific families of genes and are needed for RNA polymerase to bind to the DNA.

Where do transcription factors bind onto the DNA?

They bind onto promoter regions.

These are regions of DNA upstream of a gene which are non-coding and mostly unique to the gene.

All promoter regions have a TATA box where RNA polymerase binds to.

What are the different types of transcription factors?

• Activators - increase (ease of) transcription by helping RNA polymerase to bind

• Repressors - inhibit (ease of) transcription by blocking RNA polymerase binding

What is oestrogen an example of in gene expression?

Oestrogen is a transcriptional activator so it binds onto an activator transcription factor but doesn’t actually bind to the DNA itself.

This is because its a steriod hormone & so lipid not a protein.

How does oestrogen work?

1. Oestrogen diffuses into cell

2. It can then bind to the transcription factor ERa which is held in a protein complex

3. Its inactive without oestrogen present

4. Once oestrogen binds the ERa & oestrogen can move out of the protein complex

5. They/ERa can bind to the DNA at the right promoter

6. A cofactor can then bind & the complex formed can activate transcription

What is epigenetics?

The study of heritable changes in gene expression without changes to the DNA base sequence itself.

How does epigenetics effect gene expression?

Epigenetics involves chemical changes to the DNA and histones effecting how easily RNA polymerase can access a gene.

This means that transcription can be inhibited or increased depending on what changes have occured.

What is the epigenome?

All of the chemical modification made to the DNA and histones.

It is inherited but also changes due to environmental factors which means twins with the same inherited epigenome will have their epigenomes change in different ways.

What environemental factors can affect epigenetics/the epigenome?

• Smoking, stress, exercise and diet

• Internal signalling from the body's cells can also cause modifications to occur

What are the two processes involved in epigenetics and how are they different?

Methylation:

• Effects the DNA not the histone proteins

• Inhibits transcription

• Isn’t dynamic - once methylation has occured it can’t really/ usually isn’t reversed - much more permanent

Acetylation

• Effects the histone proteins not the DNA

• Increases transcription

• Is a dynamic change - acetylation and deacetylation both occur readily

What happens in methylation?

• Methyl groups are added onto the DNA at the cytosine base on a nucleotide

• This is carried out by enzymes called DNA MethylTransferase/DNMT

• This mostly occurs at the GC island which is a region of DNA in the promoter region but upstream of the TATA box

  • It contains many cytosines (& guanines)

How does increased methylation affect gene expression?

Methylation attracts proteins to the DNA which cause the histones to pack closer together. This makes the promoter less accessible so transcription factors & RNA polymerase as less able to bind.

This means the methylated gene is expressed less.

What is the structure of the histones?

Histones are made up of 2 layers of 4 types of proteins - total = 8 proteins.

Each of the histone proteins has an amino acid tail which can be modified by attaching groups onto them etc.

What happens in acetylation?

• Acetyl groups are added to the histone proteins on their tails by acetyl transferase

• This causes the positive charge on the histones to be reduced

• So there is less attraction between the positive histones and negative DNA

How does increased acetylation affect gene expression?

Acetylation results in less attraction between the histones & DNA so the DNA doesn’t wind around as tightly. This means the DNA is more exposed so the promoters are more accessible.

Transcription factors & RNA polymerase can bind more easily so the gene is expressed more.