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Heinrich Wilhelm Gottfried Waldeyer 1888

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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 = 10 9 - 10 10 dalton ! (for comparison a protein of 3x10 5 is considered very big. What is so special about chromosomes ?.

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what is so special about chromosomes
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 chromosomes3
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 chromosomes4
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)

slide5
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

lesson 2 chromosome structure
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 structure8
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
slide9
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.
slide10
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 structure13
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 structure21
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 structure25
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
slide28

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 structure33
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
slide37

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 structure39
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 structure45
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