Heinrich Wilhelm Gottfried Waldeyer 1888

What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 10 7 bp long = dalton ! (for comparison a protein of 3x10 5 is considered very big.

What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 10 7 bp long = dalton ! (for comparison a protein of 3x10 5 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).

What is so special about chromosomes ? 1.They are huge: One bp = 600 dalton, an average chromosome is 10 7 bp long = dalton ! (for comparison a protein of 3x10 5 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). 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)

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

Genome Complexity

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

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

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.

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.

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

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

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

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

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

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.

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

Antibodies of a person with an autoimmune disease stain centromers

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

Telomeres are like the ends of shoestrings