3.8.2.2: Regulation of transcription & translation

• Transcriptional factors:

  • have a site that binds to a specific base sequence (PROMOTER REGION) of DNA
  • Upon this binding, transcription begins at this region
  • mRNA is produced -> later translated
  • When a gene is not expressed (turned off) the binding site of the transcriptional factor that binds to DNA is inactive -> no transcription of mRNA of that gene, no translation of polypeptide OR is prevented from binding
• The hormone oestrogen as a gene expression regulator:

  • Oestrogen lipid-soluble -> diffuses simply through phospholipid bilayer of cell-surface membranes
  • In cytoplasm, oestrogen binds to receptor site of receptor molecule on transcriptional factor ->  ∴ complementary & specific shape to one other
  • -> Conformational shape change of DNA binding site on transcriptional factor -> factor activated
  • Factor can enter nucleus & bind to specific base sequences of DNA
  • -> Stimulates transcription of specific gene
• The binding of oestrogen to receptor is the same mechanism of binding of non-competitive inhibitors to an enzyme ->  ∴ binds to allosteric site
• Epigenetics involves:

  • heritable changes in gene function
  • WITHOUT changes in the DNA base sequence
• Epigenome:

  • DNA & histones covered in chemicals -> TAGS
  • Which form a 2nd layer -> EPIGENOME
  • Epigenome determines the shape of DNA-histone complex
  • Epigenome flexible -> responds to environmental changes
  • EPIGENETIC SILENCING - inactivity of genes via tightly packed arrangement caused by epigenome (∴ transcription factors cannot bind)
• DNA-histone complexes (CHROMATIN)

  
  

  Weak association:

  • DNA-histone complex less condensed
  • DNA is/more accessible to transcription(al) factors
  •  ∴ Gene is ACTIVE / switched on

  Strong association:

  • DNA-histone complex is more condensed
  • DNA less/not accessible to transcription(al) factors
  •  ∴ Gene is INACTIVE / switched off
• Changes in the environment inhibit transcription by:

  • Decreasing acetylation of histones
  • Increasing methylation of DNA
• Acetylation: acetyl group (RCH3CO) from Ace CoA

  • DECREASED acetylation -> increases +ive charge of histones -> greater electrostatic attraction between phosphate group & histones -> MORE condensation of DNA-histone complex
  •  ∴ transcription factors unable to bind to DNA
• Methylation: methyl group (CH3) bonded to cytosine in DNA

  • INCREASED methylation -> PREVENTS binding of transcription factors to DNA
  • Attracts proteins that condense DNA-histone complex (by inducing DECREASED acetylation)
• Uses of epigenetics in the treatment of diseases:

  • Uses in cancer -> preventing increased methylation + deacetylation of tumour suppressor genes
  • Uses in diagnostic therapy -> identifying level of DNA methylation & histone acetylation, acting accordingly to counteract potential effects of gene expression changes, seeking early treatment
• Process of RNAi (ribonucleic acid interference):

  • Double-stranded RNA separated into 2 single strands -> siRNA
  • 1 of the 2 strands combines with another enzyme (RISC), guiding it to mRNA molecule (of specific gene)
  • This siRNA-RISC complex binds to mRNA molecule ∵ siRNA has perfect/near perfect complementarity of base sequences to mRNA base sequences
  • Enzyme in complex cuts mRNA into shorter strands
  • Prevents mRNA from being translated by ribosome -> gene is silenced, ∴ it is switched off/inactive