14: Chromatin and Gene Expression

• histones = H2A, H2B, H3 + H4 (one in each nucleosome)
• histones are basic proteins that are positively charged and interact strongly with negatively charged dna
• acetylation of histones occurs on the e-amino groups of specific lysines at amino terminal end of all core histones

  • increases accessibility of transcription factors to DNA by opening chromatin
• deacetylases remove acetylation

  • sodium butyrate inhibits these leading to hyperacetylated histones
• methylation of histones occurs via methyl transferase onto lysines
• methylation at specific lysines of H3 signals different complexes

  • increased methylation at H3K4 = active chromatin
  • increased methylation at H3K27 = silences gene
• histones can be phosphorylated at two amino side chains

  • O phosphate linkage (serine, threonine and tyrosine)
  • N phosphate linkage (lysine, histidine, arginine)

  high levels of phosphorylation at mitosis
• DNMT1 restores CpG methylation following DNA replication so it is transmitted through cell cycle
• UHFR1 recognises DNA methylation and restores methylation on the opposing strand
• DNA methylation prevents transcription factors binding - recruits repressor complexes