Cycle 11: Epigenetics

• Epigenetics


  The study of changes in gene expression caused by external factors
• Genome


  Consists of the DNA sequence
• Epigenome


  Consists of the tags
• What tags are involved? 


  Methyl (CH3) and acetyl (COCH3) groups
• Are epigenetic tags random?

  No
• Methyl is put onto

  Specific cytosine (nucleobase), which is part of DNA
• Acetyl group is put onto


  Specific Lysine (K+, amino acid) which is part of histones
• Epigenetic tags are


  Dynamic (can be put on or off)
• What does the epigenome do?


  Controls gene expression
• Behavioural Genetics


  The study of how epigenetic alterations induced by experience and environmental stress may affect animal behaviour
• What happens to monozygotic twins with age?


  Identical genomes, difference epigenomes (due to living different lives)
• What makes a nucleosome?

  Eukaryotic DNA + Histone Protein
• What determines whether a gene can be transcribed?

  How tightly DNA is wrapped around the histone proteins
• Euchromatin (open form)


  Can transcribe
• Heterochromatin (closed form)


  Cannot transcribe
• Methylation pattern


  Only occurs on the cytosine at CpG regions
• Methylation - DNA Methyltransferase (DNMT)


  Inactivates transcription
• Demethylation - Ten-Eleven Translocation (TET)


  Activates transcription
• The tags that are stable


  Are maintained
• Transgenerational Epigenetic Inheritance


  The tags are inheritable
• Newly synthesized strands are...

  Initially unmethylated
• DNMT1 recognizes


  Hemi-methylated sites at CpG islands
• Histones are proteins with a

  Positive charge
• Why are histones positively charged?


  Because they contain lysine amino acids
• Acetylation - Histone Acetyltransferases (HATs)


  Increases transcription, euchromatin (open)
• Deacetylation - Histone deacetylases (HDACs)


  Decreases transcription, heterochromatin (close)
• Adding an acetyl group to lysine changes lysine's charge

  From positive to neutral
• Only specific lysines are

  Acetylated
• Epigenetic drift


  Describes how the epigenome changes as we age
• Yellow


  Similar methylation pattern
• Red


  Hypomethylation of 1 twin
• Green


  Hypermethylation of 1 twin
• Stress hormone in mice

  Corticosterone (called cortisol in humans)
• Glucocorticoid receptor (GR) protein binds corticosterone


  To eliminate it
• Pups grow up to raise their babies

  The same way they were raised
• Pups raised by low-grooming mothers


  Had methylation of the Nr3c1 gene, leading to decreased GR expression
• Switching the pups between mothers

  Caused a switching of tags
• Early life experiences lead to


  Inheritable, long term epigenetic effects on gene expression
• Monkey raised by bio mom

  Low anxiety, not aggressive, repulsed by alcohol
• Monkey raised by surrogate mom/ human


  High anxiety, aggressive (to monkeys and humans), alcoholics