1. Lecture #8Date _________ n Chapter 19~ The Organization and Control of Eukaryotic Genomes

2. Chromatin n Def: complex of DNA and proteins n DNA Packing histone protein (+ charged amino acids ~ phosphates of DNA are - charged) n Nucleosome ”beads on a string”; basic unit of DNA packing n Heterochromatin highly condensed interphase DNA (can not be transcribed) n Euchromatin less compacted interphase DNA (can be transcribed)

3. DNA Packing

4. Stages of gene regulation/expression n only express a small number of genes n cellular differentiation n chromatic modification n transcription n RNA processing n RNA transport n translation n protein processing and degradation

5. Chromatin Modification n Genes with highly packed heterochromatin usually not expressed n Histone acetylation – loosens heterochromatic structure enhancing transcription n Addition of methyl groups to DNA bases can reduce transcription

6. Typical Eukaryotic Gene n most eukaryotic genes have multiple control elements – segments of noncoding DNA that help regulate transcription n proximal control elements – close to the promoter n distal control elements – usually called enhancers, located further upstream than proximal control elements

7. Eukaryotic gene regulation n an activator – a protein that binds to an enhancer and stimulates gene transcription n there are no operons in eukaryotic organisms, but genes in a group will have the same regulatory sequences to coordinate expression, example heat shock response and steroid hormone action n flash movie

8. RNA Processing n different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns n flash movie

9. mRNA Degradation n longevity of mRNA affects how much protein synthesis it directs n some can last for minutes, some for weeks n degradation could begin with the removal of the 5’ cap or the poly A tail

10. Control of Translation n can repress initiation of translation n repressor proteins that bind to specific sequences or structures within the leader region at the 5’ end preventing ribosome attachment (local control) n inactivate necessary transcription factors (global control)

11. Protein Processing n many polypeptides need modified before they can properly function – addition of sugars, lipids, additional amino acids; cleaving chain into two or more pieces n can alter the targeting of a protein – if the protein cannot reach the target site, it cannot function n select a protein for degradation – attach ubiquitin, large proteasomes recognize ubiquitin and degrade the protein (could lead to cancer if cell cycle proteins become impervious to proteasomes)

12. Protein Degradation n select a protein for degradation – attach ubiquitin, large proteasomes recognize ubiquitin and degrade the protein (could lead to cancer if cell cycle proteins become impervious to proteasomes)

13. Molecular Biology of Cancer n Oncogene cancer-causing genes n Proto-oncogene normal cellular genes n How? 1-movement of DNA; chromosome fragments that have rejoined incorrectly 2-amplification; increases the number of copies of proto-oncogenes 3-proto-oncogene point mutation; protein product more active or more resistant to degradation n Tumor-suppressor genes changes in genes that prevent uncontrolled cell growth (cancer growth stimulated by the absence of suppression)

14. The Human Genome n 98.5% of the human genome does not code for protein, rRNA, or tRNA n transposable elements (jumping genes) – transposons (DNA intermediate) and retrotransposons (RNA intermediate) n simple sequence DNA – repeating units found in centromeres and telomeres n Alu elements – 300 nucleotides long, do not code for protein but many are transcribed into protein, function unknown