Role of Chromatin in Cytogenetics

Chromosome Structure

DefinitionA chromosome is an organized structure of DNA and protein

Historical Background•Walter Flemming (1882)

•Theodor Boveri (1902)•Walter Stanborough Sutton (1903)•Edmund Beecher Wilson (1905)•Theophilus Shickel Painter (1923)•Joe Hin Tjio and Albert Levan

(1956)

DNA Packaging

DNA Organization

ChromatinChromatin is the combination of

DNA and proteins that make up the contents of the nucleus of a cell.

Chromatin Function•to package DNA into a smaller

volume to fit in the cell (1.2 × 1010 miles of DNA unwound)

•to strengthen the DNA to allow mitosis

•to prevent DNA damage•to control gene expression and

DNA replication

Chromatin organization

Chromatin Organization•DNA wraps around histone proteins forming nucleosomes; the "beads on a string" structure (euchromatin).

•Multiple histones wrap into a 30 nm fibre consisting of nucleosome arrays in their most compact form (heterochromatin).

•Higher-level DNA packaging of the 30 nm fibre into the metaphase chromosome (during mitosis and meiosis).

Beads on a string

Histone Modification:

• Methylation- increases packing

• Phosphorylation – decreases packing

• Acetylation – decreases packing

Chromosome Arms

The Long and Short of it all

The position is on the chromosome's short arm (p for petit in French); q

indicates the long arm (chosen as next letter in alphabet after p).

The bands are visible under a microscope when the chromosome

is suitably stained. Each of the bands is numbered, beginning with

1 for the band nearest the centromere. Sub-bands and sub-sub-bands are visible at higher

resolution.

Centromere• Described by Flemming (1880’s) as a “primary constriction” of the chromosome

• The centromere is the part of a chromosome that links sister chromatids. During mitosis, spindle fibers attach to the centromere via

the kinetochore.

The complexity

of the centromere

…

Cohesin•Protein complex SCC1 (3p26.1)

SCC3 (3q22.3)

SMC1 (Xp11.22)

SMC3 (10q25.2)

•Regulates separation of sister chromatids

NOR• Region around which the nucleolus forms

right after cell division• Contained within the satellites on acrocentric

chromosomes• Identified using a silver stain technique-

stains satellites dark blue

Telomere - TTAGGGA telomere is a region of repetitive nucleotide sequences at each end of a

chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes

• Hermann Muller (1930’) – X-ray experiments to break and fuse chromosomes together; telomeres were resistant to breakage.

• 15,000 base pairs• Prevent chromosomes from fusing with each other

• Prevent chromosomes from loosing sequences at the ends• Usually lose 25-200 base pairs each division

• Cell senescence as soon as telomere reaches a critical length.

X- inactivation•X contains over a 1000 genes whereas Y is gene poor

•Dosage effect/ dosage compensation

•One chromosome randomly inactivates and produces a dark staining

•B_ _ _ B_ _ _ (Mary Lyon, 1961)* “random X-inactivation occurs at 6.5 days of embryogenesis”- V. najfeld

References

Lyon MF (1961) Gene action in the X-chromosome of the mouse (MusmusculusL). Nature 190: 372–373.

Diaz-Martinez, Laura Angelica; and Yu, Hongtao (December 2010) Chromosome Condensation and Cohesion. In : encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester. DOI:10.1002/9780470015902.A0022534

Cheeseman, I. M., & Desai, A. Molecular architecture of the kinetochore-microtubule interface. Nature Reviews Molecular Cell Biology 9, 33–46 (2008) doi:10.1038/nrm2310

Bednar, J., et al. Nucleosomes, linker DNA, and linker histones form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proceedings of the National Academy of Sciences 95, 14173–14178 (1998)

Fischle, W., et al. Histone and chromatin cross-talk. Current Opinion in Cellular Biology 15, 172–183 (2003)

Ford, C. E., & Hamerton, J. L. The chromosomes of man. Nature 178, 1020–1023 (1956) doi:10.1038/1781020a0