8.2.2 Regulation of transcription and translation

• What are transcription factors?

  ● Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes

  ● By binding to a specific DNA base sequence on a promoter region
• Describe how transcription can be regulated using transcription factors

  1. Transcription factors move from cytoplasm to nucleus
  2. Bind to DNA at a specific DNA base sequence on a promoter region (before / upstream of target gene)
  3. This stimulates or inhibits transcription (production of mRNA) of target gene(s) by helping or preventing RNA polymerase binding

  
• Explain how oestrogen affects transcription

  1. Oestrogen is a lipid-soluble steroid hormone so diffuses into cell across the phospholipid bilayer
  2. In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
  3. This changes the shape of the inactive transcription factor, forming an active transcription factor
  4. The complex diffuses from cytoplasm into the nucleus
  5. Then binds to a specific DNA base sequence on the promoter region of a target gene
  6. Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind
• Explain how oestrogen affects transcription

  1. Oestrogen is a lipid-soluble steroid hormone so diffuses into cell across the phospholipid bilayer
  2. In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
  3. This changes the shape of the inactive transcription factor, forming an active transcription factor
  4. The complex diffuses from cytoplasm into the nucleus
  5. Then binds to a specific DNA base sequence on the promoter region of a target gene
  6. Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind

  
• Explain why oestrogen only affects target cells

  • Other cells do not have oestrogen receptors
• Describe what is meant by epigenetics

  ● Heritable changes in gene function / expression without changes to the base sequence of DNA

  ● Caused by changes in the environment (eg. diet, stress, toxins)
• Describe what is meant by epigenome

  All chemical modification of DNA and histone proteins - methyl groups on DNA and acetyl groups on histones

  
• Explain how methylation can inhibit transcription

  1. Increased methylation of DNA - methyl groups added to cytosine bases in DNA
  2. So nucleosomes (DNA wrapped around histone) pack more tightly together
  3. Preventing transcription factors and RNA polymerase binding to promoter
• Explain the relevance of epigenetics on disease development and treatment

  ● Environmental factors (eg. diet, stress, toxins) can lead to epigenetic changes

  ● These can stimulate / inhibit expression of certain genes that can lead to disease development

  ○ Increased methylation of DNA OR decreased acetylation of histones inhibits transcription

  ○ Decreased methylation of DNA OR increased acetylation of histones stimulates transcription

  ● Diagnostic tests can be developed that detect these epigenetic changes before symptoms present

  ● Drugs can be developed to reverse these epigenetic changes
• Explain how acetylation can inhibit transcription

  1. Decreased acetylation of histones increases positive charge of histones
  2. So histones bind DNA (negatively charged) more tightly
  3. Preventing transcription factors and RNA polymerase binding to promoter
• What is RNA interference (RNAi)?


  ● Inhibition of translation of mRNA produced from target genes, by RNA molecules eg. siRNA, miRNA

  ● This inhibits expression of (silencing) a target gene

  • This happens in eukaryotes and some prokaryotes
• Explain translation by RNAi 


  1. Small interfering RNA (siRNA) or micro-RNA (miRNA) is incorporated into / bind to a protein, forming an RNA-induced silencing complex (RISC)

  ○ siRNA synthesised as double-stranded RNA → 1 strand incorporated

  ○ miRNA synthesised as a double-stranded hairpin bend of RNA → both strands incorporated

  2. Single-stranded miRNA / siRNA within RISC binds to target mRNA with a complementary base sequence

  3. Leading to hydrolysis of mRNA into fragments which are then degraded / prevents ribosomes binding

  4. Reducing / preventing translation of target mRNA into protein