3.18 Cell Specialisation

• Stem cells become specialised through differential gene expression
  
  • This means that only certain genes in the DNA of the stem cell are activated and get expressed
• Every nucleus within the stem cells of a multicellular organism contains the same genes, that is, all stem cells within an organism have an identical genome
• Despite the stem cells having the same genome, they are able to specialise into a diverse range of cell types because during differentiation certain genes are expressed ('switched' on)
• Controlling gene expression is the key to development as stem cells differentiate due to the different genes being expressed
• This differentiation occurs via the following basic steps:
  • Under certain conditions, some genes in a stem cell are activated, whilst others are inactivated
  • mRNA is transcribed from active genes only
  • This mRNA is then translated to form proteins
  • These proteins are responsible for modifying the cell (e.g. they help to determine the structure of the cell and the processes that occur within the cell)
  • As these proteins continue to modify the cell, the cell becomes increasingly specialised
  • The process of specialisation is irreversible (once differentiation has occurred, the cell remains in its specialised form)

Differential gene expression results in the differentiation of stem cells

Transcription factors control the expression of genes

• 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
• Transcription factors that increase the rate of transcription are known as activators
  • Activators work by helping RNA polymerase to bind to the DNA at the start of a gene and to begin transcription of that gene
• Transcription factors that decrease the rate of transcription are known as repressors
  • Repressors work by stopping RNA polymerase from binding to the DNA at the start of a gene, inhibiting transcription of that gene
• 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

In the example above, the transcription factor is an activator as it stimulates the transcription of the gene. Transcription factors, known as repressors, can also inhibit the transcription of genes

Operons

• In prokaryotes, control of gene expression often requires the binding of transcription factors to operons
• An operon is a section of DNA that includes:
  • A cluster of structural genes that are transcribed together (these code for useful proteins e.g. enzymes)
  • Control elements, including a promoter region (a DNA sequence that RNA polymerase initially binds to) and an operator region (where transcription factors bind)
  • Some operons may include regulatory genes that code for activators or repressors

The lac operon

• Structural genes in prokaryotes can form an operon: a group or a cluster of genes that are controlled by the same promoter
• The lac operon found in some bacteria is one of the most well-known of these
• The lac operon controls the production of the enzyme lactase (also called β-galactosidase) and two other structural proteins
• Lactase breaks down the substrate lactose so that it can be used as an energy source in the bacterial cell
• It is known as an inducible enzyme (this means it is only synthesized when lactose is present)
• This helps the bacteria avoid wasting energy and materials

Structure of the lac operon

• The components of the lac operon are found in the following order:
  • Promoter for structural genes
  • Operator
  • Structural gene lacZ that codes for lactase
  • Structural gene lacY that codes for permease (allows lactose into the cell)
  • Structural gene lacA that codes for transacetylase
• Located to the left (upstream) of the lac operon on the bacterium's DNA there is also the:
  • Promoter for regulatory gene
  • Regulatory gene lacI that codes for the lac repressor protein
• The lac repressor protein has two binding sites that allow it to bind to the operator in the lac operon and also to lactose (the effector molecule)
  • When it binds to the operator it prevents the transcription of the structural genes as RNA polymerase cannot attach to the promoter
  • When it binds to lactose the shape of the repressor protein distorts and the repressor protein can no longer bind to the operator

The components of the lac operon along with the upstream regulatory gene and its associated promoter

When lactose is absent

• The following processes take place when lactose is absent in the medium that the bacterium is growing in:
  • The regulatory gene is transcribed and translated to produce lac repressor protein
  • The lac repressor protein binds to the operator region upstream of lacZ
  • Due to the presence of the repressor protein RNA polymerase is unable to bind to the promoter region
  • Transcription of the structural genes does not take place
  • No lactase enzyme is synthesized

The repressor protein binds to the operator region of the lac operon and prevents transcription of the structural gene

When lactose is present

• The following processes take place when lactose is present in the medium that the bacterium is growing in:
  • There is an uptake of lactose by the bacterium
  • The lactose binds to the second binding site on the repressor protein, distorting its shape so that the repressor protein cannot bind to the operator region
  • RNA polymerase is then able to bind to the promoter region and transcription takes place
  • The mRNA from all three structural genes is translated
  • The enzyme lactase is produced and lactose can be broken down and used for energy by the bacterium

The binding of lactose to the repressor protein frees up the operator region of the lac operon so RNA polymerase can bind and begin transcription of the structural genes