Heinrich Wilhelm Gottfried Waldeyer 1888

1. Heinrich Wilhelm Gottfried Waldeyer 1888

2. What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 107 bp long = 109-1010 dalton ! (for comparison a protein of 3x105 is considered very big.

3. What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 107 bp long = 109-1010 dalton ! (for comparison a protein of 3x105 is considered very big. 2. They contain a huge amount of non- redundant information (it is not just a big repetitive polymer but it has a unique sequence) .

4. What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 107 bp long = 109-1010 dalton ! (for comparison a protein of 3x105 is considered very big. 2. They contain a huge amount of non- redundantinformation(it is not just a big repetitive polymer but it has a unique sequence) . 3. There is only one such molecule in each cell.(unlike any other molecule when lost it cannot be re-synthesized from scratch or imported)

5. Philosophically - the cell is there to serve, protect and propagate the chromosomes. • Practically - the chromosome must be protected at the ends - telomers and it must have “something” that will enable it to be moved to daughter cells - centromers

6. Genome Complexity

7. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

8. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

9. Take 4 meters of DNA (string) and compact them into a ball of 10M. Now 10M are 1/100 of a mm and a bit small to imagine – so now walk from here to the main entrance let say 400 meters and try to compact it all into 1 mm.

10. This compaction is very complex and the DNA isn’t just crammed into the nucleus but is organized in a very orderly fashion from the smallest unit - the nucleosome, via loops, chromosomal domains and bands to the entire chromosome which has a fixed space in the nucleus.

13. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

21. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Telomeres • Centromeres

25. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

28. SARs are very AT-rich fragments several hundred base pairs in length that were first identified as DNA fragments that are retained by nuclear scaffold/matrix preparations. They define the bases of the DNA loops that become visible as a halo around extracted nuclei and that can be traced in suitable electron micro-graphs of histone-depleted metaphase chromosomes. They are possibly best described as being composed of numerous clustered, irregularly spaced runs of As and Ts

33. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

37. R-bands are known to replicate early, to contain most housekeeping genes and are enriched in hyperacetylated histone H4 and DNase I-sensitive chromatin. This suggests they have a more open chromatin conformation, consistent with a central AT-queue with longer loops that reach the nuclear periphery. In contrast, Q-bands contain fewer genes and are proposed to have loops that are shorter and more tightly folded, resulting in an AT-queue path resembling a coiled spring.

39. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Centromeres

44. Antibodies of a person with an autoimmune disease stain centromers

45. Lesson 2 - Chromosome structure • The DNA compaction problem • The nucleosome histones (H2A, H2B, H3, H4) • The histone octamere • Histone H1 the linker histone • Histone modification • Higher order compactions • Chromatin loops and scaffolds (SAR) • Non histone chromatin proteins • Heterochromatin and euchromatin • Chromosome G and R bands • Telomeres • Centromeres

46. Telomeres are like the ends of shoestrings