8.2.5 Regulation of Transcription

• Eukaryotes use transcription factors to control gene expression
• A transcription factor is a protein that controls the transcription of genes by binding to a specific region of DNA
• They ensure that genes are being expressed in the correct cells, at the correct time and to the right level
• It is estimated that ~10% of human genes code for transcription factors
  • There are several types of transcription factors that have varying effects on gene expression
  • This is still a relatively young area of research and scientists are working hard to understand how all the different transcription factors function
  • Transcription factors allow organisms to respond to their environment
  • Some hormones achieve their effect via transcription factors

The structure of a gene

• 'Upstream' refers to the DNA before the start of the coding region
• The promoter is a section of DNA upstream of the coding region that is the binding site for proteins that control the expression of the gene, including:
  • RNA polymerase
  • Transcription factors

• While DNA is translated in the 3' to 5' direction, it is transcribed in the 5' to 3' direction to produce messenger RNA (mRNA)

How transcription factors work

• Transcription factors are proteins that enter the nucleus from the cytoplasm through nuclear pores
• Transcription factors are activated through a signalling pathway that usually starts from outside the cell
• Some transcription factors bind to the promoter region of a gene
  • This binding can either allow or prevent the transcription of the gene from taking place
  • Transcription factors interact with RNA polymerase, either by assisting RNA polymerase binding to the gene (to stimulate expression of the gene) or by preventing it from binding (to inhibit gene expression)

• Therefore, the presence of a transcription factor will either increase or decrease the rate of transcription of a gene
• For example, oestrogen is a hormone, found in mammals, that works as a transcription factor alongside specific proteins that activates the transcription of many genes

In the example above the transcription factor stimulates the transcription of the gene. Transcription factors can also inhibit the transcription of genes.

Oestrogen

• Oestrogen is a steroid hormone found in mammals
  • Steroid hormones are small, hydrophobic, lipid-based hormones that can diffuse through the cell membrane and can pass directly into the nucleus through nuclear pores

• Oestrogen is involved in controlling the female fertility cycle and is also responsible for stimulating sperm production in males
  • Up to 100 different genes are controlled by oestrogen

• The oestrogen stimulation pathway:

  1. Oestrogen diffuses through the cell surface membrane into the cytoplasm
  2. Oestrogen diffuses through a nuclear pore into the nucleus
  3. Within the nucleus, oestrogen attaches to an ERα oestrogen receptor that is held within a protein complex, this causes the ERα oestrogen receptor to undergo a conformational change
  4. The new shape of the ERα oestrogen receptor allows it to detach from the protein complex and diffuse towards the gene to be expressed
  5. The ERα oestrogen receptor binds to a cofactor which enables it to bind to the promoter region of the gene, this stimulates RNA polymerase binding and gene transcription

The oestrogen stimulation pathway