Heinrich Wilhelm Gottfried Waldeyer 1888

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.

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) .

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) .

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 10M. Now 10M 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