imprinting genes

• Genomic imprinting


  An epigenetic process that modifies the activation of genes, not the genetic makeup
• Genomic imprinting


  • Genes are tuned on or off depending if they are inherited from mum or dad
  • Individuals receive one copy of each gene from mum or dad
  • The mother or the father's gene is inactivated, meaning only one is on
• DNA methylation


  1. Cytosines can be methylated at the 5th group by DNA methyltransferase

  2. The methyl group is a tag that ensures the copy of the gene stays off

  3. Methylation prevents transcription factors binding and recruits methyl binding proteins that make the gene inaccessible and tightly compacted

  4. This remains the same in all cells through the life of the cells

  5. Only reset in the germ cells
• Mules and Hinnies


  • Mules (female horse x male donkey) are very reliable and calm
  • Hinnies (female donkey x male horse) have a terrible temperament and are not good for domestication
• Genomic imprinting does not depend on gender, it depends on the parent of origin
• Ligers and Tigons


  • Ligers (male lion x female tiger) tend to be larger and heavier than their parent species
  • Tigons (female lion x male tiger) are the same size as their parents
• Reason for size difference between ligers and tigons

  • Ligers are larger because the paternal lion genome wants to ensure its offspring is bigger than others for survival, while the maternal tiger genome does not have defences against this
  • Tigons are the same size as their parents because the maternal lion genome has the ability to control cub size
• Liger and tigon are portmanteaus of the words lion and tiger
• Foetal-maternal conflict (war in the womb)


  For the vast majority of genes, the paternal and maternal genomes cooperate to make a healthy human, but sometimes there is conflict due to nutrients and behaviour
• Both paternal and maternal genes are essential for embryo development
• Evidence for genomic imprinting

  • Gynogenetic diploids (two female pronuclei) resulted in an inviable embryo, while androgenetic diploids (two male pronuclei) could develop to term
  • Control embryos from a paternally-derived pronucleus and maternally-derived pronucleus developed normally
  • Imprinting is essential for normal development in mammals
• IGF-II imprinting


  The maternal copy of the IGF-II gene is silenced, so the phenotype is controlled by the paternal copy
• IGF-II imprinting in mice

  • Heterozygous mice with the mutant IGF-II allele from the father are growth-deficient, while those with the mutant allele from the mother are normal size
  • Only the paternal allele of IGF-II is expressed in embryos, while the maternal allele is silent
• IGF-II imprinting is a classical model for studying imprinting in mammals
• Zygous siblings

  Siblings that share the same genotype
• Only the paternal allele is expressed in embryos, while the maternal allele is silent – shown through in Situ hydr
• This is the classical model for imprinting gene in mammals
• The IGF-II locus has since been studied in great detail and a lot of our current knowledge comes from manipulation of this system
• This is now a model for studying imprinting – most of the molecular details of imprinting in mammals is based on mouse studies mice that carry a targeted disruption of the gene encoding insulin-like growth factor II (IGF- II)
• Transmission of this mutation through the male germline results in heterozygous progeny that are growth deficient. In contrast, when the disrupted gene is transmitted maternally, the heterozygous off- spring are phenotypically normal
• The difference in growth phenotypes depends on the type of gamete contributing the mutated allele
• Homozygous mutants are indistinguishable in appearance from growth-deficiency heterozygous siblings
• Nuclease protection and in situ hybridization analyses of the transcripts from the wild-type and mutated alleles indicate that only the paternal allele is expressed in embryos, while the maternal allele is silent
• Key finding


  In mice the paternal and maternal members of some autosomal gene pairs are functionally non-equivalent
• Chromatin states that govern gene activity

  • Euchromatin
  • Heterochromatin
• Heritable chromatin states help the gene know if this maternal or paternal
• One copy of the gene is silenced in a permanent way
• The allele has to remember through if it's paternal or maternal and this is from chromatin states
• Euchromatin


  Chromosome material which does not stain strongly except during cell division. It represents the major genes and is involved in transcription
• Heterochromatin


  Chromosome material of different density from normal (usually greater), in which the activity of the genes is modified or suppressed
• Histone acetyl-transferase (HAT)

  Targets H3 tail
• H3K14ac


  A docking site for Bromo-domain proteins; stimulates nucleosome accessibility so this is for open chromatin for gene expression
• HDAC

  Represses the active states by removing acetylate and can be reversed by histone deacetylases
• Histone lysine methyltransferases (KMT)

  Methylates H3 tail
• H3K9me3


  Provides docking site for heterochromatin protein 1 (HP1); Impairs nucleosome accessibility which closes the chromatin to prevent gene expression
• Antisense RNA is important for turning off one gene
• The molecular hallmarks of epigenetic control
• DNA methylation is the molecular basis of epigenetic silencing
• Only a restricted subset of genes is expressed in any one cell, and that subset is characteristic for each cell type at particular times in its life cycle
• Genes differ in the pattern of chemical modification to certain cytosine bases in the DNA, lacking methyl groups that are present on non‐expressing genes: differences in the DNA methylation patterns