Lecture outline

Chromatin structure/ genome organization

• DNA-protein complex called chromatin, packaged into a condensed structure
  • nucleosomes- (beads on a string)- consist of DNA wound around protein core of histones
  • beaded string coils to form 30 nm chromatin fiber
  • 30 nm fiber forms looped domains
  • looped domains coil and fold to form compact chromosome
• heterochromatin- highly condensed, not transcribed
• euchromatin- less condensed, transcribed
• Genome organization at DNA level
  • most DNA does not encode protein or RNA regulatory sequences, introns, repetitive DNA (tandem repeats (satellite DNA), interspersed repetitive DNA)
  • gene families- collection of identical or very similar genes
  • gene amplification- selective replication of certain genes
  • rearrangement in genome- transposons, immunoglobulin genes
• Control of gene expression
  • chromatin modifications- DNA methylation, histone acetylation
  • transcription initiation- promoter, DNA control elements, transcription factors
  • post-transcriptional mechanisms- regulation of mRNA degradation, protein processing and degradation
• Molecular biology of cancer
  • oncogenes- cancer-causing genes
  • proto-oncogenes- cellular genes involved in normal cell growth and division
  • proto-oncogene can become an oncogene
    • movement of DNA within genome
    • amplification of proto-oncogene
    • point mutation in proto-oncogene, e.g. ras- point mutation in ras leads to hyperactive version of Ras protein
  • tumor suppressor genes- genes whose normal products inhibit cell division, e.g. p53 gene- encodes tumor suppressor protein

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