Control of Gene Expression


Gene Regulation

  • Housekeeping genes are those that code for enzymes which are necessary for reactions present in metabollic pathways
  • Protein-based hormones are only required by certain cells at certain times to carry out a short-lived response, they are coded for by tissue-specific genes. 
  • The entire genome of an organism is present in any cells which contains a nucleus. 
  • Gene expression enables bacteria to respond to changes in their environment
  • Fundamentally gene regulation is the same in both eukaryotes and prokaryotes. But in eukaryotes the stimulus that changes gene expression is much more complex in eukaryotes. 
  • There are a number of different ways in which genes ccan be regulated: 
    • Transcriptional: genes can either be turned on or off
    • Post-transcriptional: mRNA can be modified which regulates translation and the types of proteins which are produced. 
    • Translational: translation can be either stopped or started
    • Post-Translational: Proteins can be modified after synthesis, this changes their function. 
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Transcriptional Control

There are a number of mechanisms that can affect the transcription of genes:

  • Chromatin remodelling
  • Histone modification
  • Lac Operon
  • Role of cyclic AMP
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Chromatin Remodelling

  • A chromatin is the DNA/protein complex formed when DNA is wound around histones. 
  • Heterochromatin is tightly wound DNA which causes chromosomes to be seen during cell division.
  • This is different to euchromatin which is loosely wound DNA that is present during interphase. 
  • When DNA is wound tightly the transcription of genes is not possible, this is becauase RNA polymerase can access the genes. 
  • In euchromatin, the genes are able to be freely transcribed. 
  • Therefore, protein synthesis does not occur during cells division but instead occurds during interphase between cell divisions. 
  • This ensures that the proteins necessary for cell division are synthesised in time. 
  • If it occured when cells were actually dividing it would be a much more complex, energy consuming process. 
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Histone Remodelling

  • DNA is negatively charged and histones are positively charged, this is why DNA coils around the histones. 
  • It is possible to modify histones so that the degree of packing can be either increased or decreased. 
  • Acetylation is the addition of acetyl groups 
  • Phosphorylation is the addition of phosphate groups. 
  • Methylation is the addition of methyl groups
  • Acetylation and phosphorylation can reduce the positive charge on the histones, this will make them more negative. As a result of this the DNA will coil less tightly. 
  • When DNA coils less tightly certain genes can be transcribed. 
  • Methylation makes the histones more hydrophobic, the result of this is that they bind more tighty to each other, this means that the DNA coils more tightly and the trancription of genes is prevented. 
  • Epigenetics describes this control of gene expression by the modification of DNA. It is sometimes used to include all of the different ways in which gene expression is regulated. 
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Lac Operon

  • Lac Operon is a group of genes which are under the control of the same regulatory mechanism. They are also expressed at the same time. Operons are more common in prokaryotes than they are in eukaryotes, this is due to the smaller and more simple structure of their genomes. 
  • Operons are an efficient way of saving resources because if certain gene products are not required then the genes involved in producing them can all be switched off. 
  • Glucose is the preferred respiratory substrate of E.Coli. It is easier to metabolise. If glucose is in short supply then lactose can be used instead, to do this different enzymes are required to metabolise lactose. 
  • The Lac Operon consists of three genes: lacZ, lacY and lacA, all are involved in the production of lactose. They are structural genes, coding for three enzymes: beta-galactosidase, lactose permease and transactylase.
  • All three enzymes are transcribed onto one single long molecule of mRNA. 
  • lacI is a regulatory gene, it is location near to the operon and codes for a repressor protein. 
  • This pressor proteins prevents the transcription of the strucutral genes in the absence of lactose. 
  • The repressor protein is constantly produced and binds to the operator, this is close to the structural genes. 
  • This binding prevents RNA polymerase binding to DNA and stops transcription. This is down regulation. 
  • The section of DNA which is the binding site for RNA polymerase is the promoter region. If lactose is present it binds to the repressor protein changing its shape, it can't bind to the operator. RNA polymerase can bind to the operator, the three structural genes are transcribed and enzymes are synthesised.
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Role of Cyclic AMP

  • The binding of RNA polyermase stil results in the slow rate of trancription which must be increased or up-regulated in order to procude the quantity of enymes needed to efficiently metabolise lactose. 
  • This is done by the binding of another protein, cAMP receptor protein (CRP).
  • This is only possible when CRP is bound to cAMP.
  • The transport of glucose into a cell of E.Coli decreases the levels of cAMP. 
  • As a result of this the transcription of genes responsible for the metabolism of lactose is reuces. 
  • If both glucose and lactose are present then it will still be glucose, this is the preferred respiratory substrate which is metabolised. 
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Post- Transcriptional/Pre-Translational control

RNA processing

  • pre-mRNA, is a precursor molecule, it is the product of transcription. 
  • mature mRNA is formed from the modification of pre-mRNA, this necessary before it can bind to a ribosome and code for the synthesis of the required protein. 
  • A cap is a modified nucleotide. 
  • A tail is a long chain or adenine molecules
  • One cap is added to the 5' end of the chain and one tail is added to the 3' end of the chain. These help to stabilise mRNA and delay degradation in the cytoplasm.
  • The cap aids the binding of mRNA to ribosomes.
  • Splicing occurs where RNA is cute at specific points, the introns (non-coding DNA) and exons (coding DNA) are joined. These processes occur within the nucleus. 

RNA editing

  • The base seuqence of some mRNA can be changed through base addition, deletion or substitution. They have the same effect as point mutations, resultting in the synthesis of alternative proteins that can have different functions. 
  • This increases the range of proteins which can be made from a single mRNA molecule or gene. 
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Translational Control

The following mechanisms regualte the process of protein synthesis:

  • degradation of mRNA- the more resistant the molecule the longer it will last in the cytoplasm, so a greater quantity of protein will be synthesised
  • binding of inhibitory proteins to mRNA prevents it binding to ribosomes and the synthesis of proteins 
  • activation of initiation factors that aid the binding of mRNA to ribosomes
  • Protein Kinases 
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Protein Kinases

  • Protein Kinases are ezymes which catalyse the addition of phosphate groups to proteins, 
  • The addition of a phosphate group changes the tertiary structure and so the function of a protein.
  • Phosphorylation is able to activate many proteins, therefore protein kinases are important regulators of cell activity 
  • cAMP is the secondary messenger which often activates protein kinases. 
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Post-Translational Control

Post-Translational control involves the modification of proteins which have been synthesised, they include: 

  • the addition of non-protein groups e.g. carbohydrate chains, lipids or phosphates
  • modifying amino acids and the formation of bonds like disulphide bridges. 
  • folding or shortening of proteins 
  • modification by cAMP e.g. in the Lac Operon cAMP binds to the cAMP receptor proteins, this increases the rate of transcription of structural genes.  
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