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Organization of the eukaryotic genomes

Organization of the eukaryotic genomes. Chromatin structure Genome organization. Why do eukaryotes need to form chromatin? Levels of packing: - role of histones - nucleosomes Euchromatin and heterochromatin. Genome organization. Prokaryotes Most genome is coding

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Organization of the eukaryotic genomes

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  1. Organization of the eukaryotic genomes Chromatin structure Genome organization

  2. Why do eukaryotes need to form chromatin? Levels of packing: - role of histones - nucleosomes Euchromatin and heterochromatin

  3. Genome organization • Prokaryotes • Most genome is coding • Small amount of non-coding is regulatory sequences • Eukaryotes • Most genome is non-coding (95%) • Regulatory sequences • Introns • Repetitive DNA

  4. Repetitive DNA • Two types • Tandemly repetitive • Interspersed repetitive • Tandemly repetitive • Satellite DNA • 1-10bp, repeated up to several hundred thousand times • Three types • Associated with diseases • Centomeres and telomeres

  5. Repetitive DNA • 100s-1000s bp long found throughout the genome • Similar but not identical • Alu elements • Transcribed into RNA • Function unknown

  6. Multigene families • Collection of identical or similar genes • Derived from a single ancestral gene • Clustered or dispersed throughout the genome • Identical genes • Examples include: rRNA and histone genes • Nonidentical genes • globin genes (a and b)

  7. Transposons • Genes sequences that can move around in a genome • 10% of the human genome • Most are retrotransposons

  8. Control of eukaryotic gene expression Types (levels) of control - chromatin structure - transcriptional initiation - post-transcriptional mechanisms

  9. Why is regulation so important in eukaryotic cells?

  10. Levels of control

  11. Chromatin modifications • Gene expression can be regulated at the level of chromatins structure • DNA methylation • Addition of –CH3 groups to DNA bases • Inactive DNA is highly methylated, active unmethylated • Demethylation can turn genes on • Methylation patterns are stable and heritable • Genomic imprinting (methylation turns maternal or paternal genes off during development)

  12. Histone acetylation • addition of an acetyl group -COCH3 • Acetylated histones grip DNA less tightly, providing easier access for transcription proteins in this region. • Histone acetylases and deacetylases – associated or part of transcription factors

  13. Transcriptional initiation • DNA control elements • Transcription factors

  14. Transcriptional activators

  15. Post-transcriptional mechanisms • RNA processing • RNA stability • Prok’s: few minutes • Euk’s: hours to days • Degradation starts at poly A tail • Stability elements located in 3’UTR of mRNA • Translational initiation • Polypeptide processing • Protein degradation

  16. Cancer Cancer is a disease in which cells escape from the control methods that normally regulate cell growth and division.

  17. Causes? • Change in expression of genes involved in regulating normal cell growth and division, called proto-oncogenes • Mutations in genes that normally inhibit cell division, called tumor-suppressor genes

  18. Proto-oncogenes • Oncogenes are cancer causing genes • Proto-oncogenes are genes that encode proteins involved in normal cell growth and division. How do they become oncogenes?

  19. Cancer results from a buildup of multiple mutations Usually at least 12 DNA changes include activation of at least one oncogene inactivation of at least one tumor suppressor

  20. Other facts • Can inherit predisposition to a certain type of cancer – mutations in genes (repair pathways) • Viral infections (retroviruses) can result in some cancers (15% in humans) • Integration into genome • disrupts tumor sup. gene • bring in new oncogene within its genome • Telomerase enzyme is activated

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