The Eukaryotic Genome

• The human genome has 22 pairs of autosomes and 1 pair of sex chromosomes
• The X chromosome is bigger than the Y chromosome
• Eukaryotes have a huge genome, but only a small proportion of it codes for proteins
• centromeres and telomeres have highly repetitive sequences
• We can look at the variable number tandem repeats in a repetitive sequence through PCR
• Most protein-coding genes only have one copy
• Gene families come from duplication of a single gene
• Gene families have similar sequence and function
• the globin family is a gene family
• DNA is wound around proteins called histones to form nucleosomes
• Histone tails have lots of arginine and lysine, which are positively charged at physiological pH
• histones can form electrostatic interactions with the negative phosphate backbone of DNA, independent of its sequence
• Histones shield the negative charges of the phosphates, allowing DNA to bend and wrap
• The ends of chromosomes contain telomeres to protect the information at the ends
• Histone restricts transcription
• The centromere is the region where the sister chromatids attach
• The p arm is the short arm of the chromosome
• The q arm is the long arm of the chromosome
• Chromatin is the complex of DNA and proteins
• Condensed DNA is harder for proteins such as transcription factors to access
• Heterochromatin: More condensed, so less transcription is occurring
• Euchromatin: Less condensed, so more transcription is occurring
• DNA isn't always packed tightly into chromosomes
• Modifying histone tails can remove the charge, enabling proteins to bind
• Some proteins can recognise modifications and interact with histones
• HATs acetylate lysine to remove the positive charge of the histone tail
• HAT = histone acetyltransferase
• Acetylation of histones causes DNA to be wound less tightly, meaning that is more accessible to initiate transcription
• Some proteins can also bind to acetylated lysine
• HDACs reverse the acetylation of histone tails, reducing transcription
• HDAC = histone deacetylases
• HMTs methylate lysine or arginine on the histone tail
• HMT = histone methyltransferases
• Some proteins can bind to these methylated residues
• Histone demethylases remove the methyl group from the histone tail
• In specific cells, regions of the chromosome that aren't required will be packaged tightly and not accessed
• The packaging of chromosomes affects the expression of proteins
• Cells only express proteins relevant to their functions
• Induced pluripotent stem cells

  1. Modify histones
  2. Introduce transcription factors
  3. Expression of genes required for pluripotency