My topic 8

• What is epigenetics?

  Epigenetics is the heritable change in gene function without changing the DNA base sequence
• What factors can add epigenetic tags?

  Diet, Stress and toxins
• What is the epigenome?


  A single layer of chemical tags on the DNA
• What does the epigenome do?

  Impacts the shape of the DNA-histone complex and whether DNA is tightly wound so won't be expressed or unwound so it will be expressed
• What happens if DNA is tightly wound?

  Transcription factors cannot bind, therefore the epigenome which is due to changes in the environment can inhibit transcription
• Tightly coiled chromatin = heterochromatin
• Less tightly coiled DNA = euchromatin
• Where does a methyl group always attach?

  CpG site - where cytosine and guanine bases are next to each other (linked by phosphodiester bond)
• What does increased methylation do?

  Changes the DNA structure to make it more tightly packed and condensed (heterochromatin) so it can't interact with the gene so its not expressed (switched off)
• Why does methyl bind to DNA ?

  Methyl has slight +ve charge and DNA has slight -ve charge therefore they attract and become more condensed
• What does decreased acetylation do ?

  Inhibits transcription
• Why does decreased acetylation decrease transcription?

  DNA histones become more +ve and are more attracted to -ve phosphate group on DNA. So DNA and histones are more strongly associated making it hard for transcriptional factors to bind
• What causes heterochromatin?

  Increased methylation

  Decreased acetylation
• What causes euchromatin?

  Decreased methylation

  Increased acetylation
• What are tumour suppressor genes ?

  These genes produce proteins to slow down cell division and cause cell death if DNA copying errors are detected
• What happens if there is a mutation in the TSG?


  TSG would not produce proteins so cell division would continue and mutated cells would not be identified and destroyed - linked to cancer
• What happens if there is hypermethylation of the TSG?

  Gene is inactive and switched off
• What happens if an oncogene is hypomethylated?

  Gene permenantly switched on (permenant mitosis)
• What is transcription control?

  Transcription of target genes can be inhibited or stimulated when specific transcription factors move from the cytoplasm to the nucleus (site of transcription). This can turn genes on/off
• What are transcription factors?

  These are proteins which bind to different base sequences on DNA and therefore initiate transcription of genes
• What happens without a TF bound?

  The gene is inactive and the protein wont be made
• What is oestrogen ?

  A steroid hormone that can initiate transcription
• How does oestrogen initiate transcription?

  Oestrogen binds to a specific receptor site on a transcriptional factor. When it binds it changes the TFs shape and makes it complementary and able to bind to the DNA to initiate transcription
• What is translation control ?

  Regulation of gene expression - regulation translation of mRNA
• Where can transcriptional control occur?

  Eukaryotes
• Where can translational control occur?

  Eukaryotes + Prokaryotes
• What is RNA interference (RNAi)?


  Process of regulating translation. This is when mRNA molecule that has already been transcribed gets destroyed before it is translated to create a polypeptide chain
• What is RNAi done by?

  Small interfering RNA (siRNA)
• Process of RNA interference

  1. double stranded siRNA is cut into siRNA by an enzyme
  2. one strand of the siRNA then combines with another enzyme
  3. siRNA-enzyme complex will bind via complementary base pairing to another mRNA molecule
  4. once bound the enzymes cut the mRNA up into fragments so it can no longer be translated
  5. fragments move into a processing body where they are degraded (similar process happens with miRNA in plants)
• What is cancer?

  Cancer is a result of mutations in the genes that regulate mitosis. If genes mutate and non-functioning proteins are made then mitosis is not regulated and results in uncontrollable division of cells and the creation of a tumour
• Benign tumours

  • grow very large but at a slow rate
  • non-cancerous - because they produce adhesion molecules which stick them together and to a particular tissue
  • often surrounded by capsule so remain compact
  • can be removed by surgery
  • rarely returns
  • impact is localised and often non-threatening depending on location
• Malignant tumours

  • cancerous
  • grow rapidly
  • cell nucleus becomes large and cell can become unspecialised again
  • do not produce adhesive molecules so metastasis occurs - the tumour breaks off and spreads to other parts of the body
  • is not encapsulated so can grow projections into surrounding tissues and develop its own blood supply
  • can be life threatening
  • removal of tumour is hard - treatment like radiotherapy or chemotherapy is needed
  • reaccurance more likely
• What causes the development of a tumour?

  Gene mutation in either TSG and/or oncogene, the abnormal methylation of TSG and oncogenes or increased oestrogen concentrations
• What are oncogenes?


  The mutated version of proto-oncogenes
• What is a proto-oncogene?

  creates a protein involved in initiation of DNA replication and mitosis cell division when body needs new cells
• Oncogene mutations?


  Result in this process (role of proto-oncogene) being permanently activated to make cells divide continually
• What are tumour suppressor genes?

  Genes that produce proteins to slow down cell division to cause cell death if DNA copying errors are detected. If a mutation results in TSG not producing proteins cell division would continue and mutated cells would not be identified or destroyed
• What happens if a TSG is hypermethylated?

  Gene inactive and is switched off therefore cell division is not controlled and mutated cells are not identified or destroyed
• What happens if an oncogene is hypomethylated?

  Gene permanently switched on so cell division is continually occuring
• Increased oestrogen concentrations and tumours ?

  After menopause, oestrogen is made in the fat cells in the breast tissue, this can result in a tumour being produced as oestrogen can bind to TFs to initiate transcription and therefore cell division. The tumour results in even more oestrogen being produced which then increases tumour size and attracts WBCs which further increase tumour size