Chromosome structure

• Chromatin: The complex of DNA and proteins within the nucleus of a eukaryotic cell. The material of which chromosomes are made from.
• Chromatid: One of the two copies of a replicated chromosome that is joined at the centromere to the other copy. The two identical chromatics are called sister chromatids.
• Centromere: the chromosomal region that holds sister chromatids together and where the kinetochore forms.
• Kinetochore: A protein complex that forms on chromosome centromere during M (mitosis) phase that binds microtubules and direct chromosome movement in mitosis.
• Telomeres: The end of chromosomes.
• DNA is packaged with proteins called histones to form chromatin.
• Genes are transcribed to produce the RNA molecules needed to programme translation (protein synthesis) in the cytoplasm.
• The sequence of bases in the DNA encode every protein and genetic trait.
• In eukaryotic cells, the genetic material is split into individual long pieces of double-stranded DNA called chromosomes.
• Individual eukaryotic chromosomes contain either:

  ~A single DNA molecule (before DNA replication)

  ~Or two identical DNA molecules (after DNA replication).
• 1. At the simplest level, chromatin is a double-stranded helical structure of DNA.
  2. DNA is complexed with histones to form nucleosomes.
  3. Each nucleosome consists of eight histone proteins (H2A,H2B, H3, and H4) x2 which the DNA wraps 1.65 times around.
  4. A chromatosome consists of a nucleosome plus the H1 histone.
  5. The nucleosomes fold up to produce a 30-nm fibre...
  6. ... that firms loops averaging 300nm in length.
  7. The 300-nm fibres are compressed and folded to produce a 250-nm wide fibre.
  8. Tight coiling of the 250-nm fibre produces the chromatid of a chromosome.
• Chromosomes undergo dramatic reorganisation (condensation/compaction) when cells divide.
• Chromosomes can be classified according to the position of their centromere.

  ~Near the centre- metacentric

  ~Towards one end- acrocentric

  ~Right at one end- telocentric.
• Organisation of eukaryotic chromosomes;

  ~Metaphase chromosomes (in mitosis) are highly compacted.

  ~Interphase chromosomes are visible less distinct and exhibit variable levels of compaction depending on their activity.

  -Euchromatin: Largely de-compacted and potentially active in gene expression.

  -Heterochromatin: Highly compacted and transcriptionally inactive (in general).
• Some heterochromatin regions contain very few or no genes and instead form key structures such as centromeres or telomeres that contain receptive DNA sequences.
• DNA is coiled around a protein core to from nucleosomes.

  ~One nucleosome= 147 bp of double stranded DNA wrapped around a protein core of 8 histone proteins (octamer).

  ~Nucleosomes ever ~200 bp.

  ~In euchromatin the wrapping is loose (DNA and histone) so that the raw DNA may be accessed.
• Chromatin can adopt a series of higher order structures as it becomes more compact; a process known as condensation.

  
  

  Chromatin condensation involves a fifth histone protein: histone H1.
• Many other proteins are associated with the higher order structures of chromatin- these form the chromosome scaffold.
• Individual chromosomes compartmentalise in the nucleus, they concentrate within discrete territories with limited intermingling, even in interphase.
• Euchromatin vs. heterochromatic.

  The kinds of chromatin are visible during interphase:

  ~Euchromatin: Diffuse and light-staining; actively transcribed genes; tend to concentrate to the middle of the nucleus.

  ~Heterochromatin- condensed, dark-staining, genes not transcribed (reduced accessibility); repetitive sequences; tend to concentrate at the periphery.
• Regulating DNA accessibility is one mechanism by which gene expression can be controlled.
• Points for the regulation of gene expression in eukaryotes:

  ~Gene expression must be regulated to ensure proper timing and location of protein production.

  ~Regulation can occur at multiple points.

  ~Remodelling of chromatin (increased DNA accessibility) for transcription.
• Nucleosomes contain DNA and histones in a tight complex, compacting and making DNA less accessible.
• Nucleosomes are dynamic and transcription factors can bind to DNA in the nucleosome.

  Eukaryotic cells have a large variety of histone modifying enzymes that covalently modify chromatin structure and ATP-dependent chromatin remodelling complexes, to permit DNA replication and transcription.
• Chromatin remodelling: Covalent modifications.

  ~Each histone has a positively charted amino acids 'tail' at its N terminus.

  ~Histone acetyltransferases (HATs) can change the tails charge by adding acetyl groups to lysine residues (HDACs remove them).

  ~This opens up the nucleosomes, increasing DNA accessibility, facilitates transcription factor binding and recruitment of chromatin remodellers and activates transcription.
• Chromatin remodelling: ATP-dependent remodellers.

  Possible mechanisms for increased local access include:

  ~Nucleosome sliding.

  ~Nucleosome displacement.

  ~Partial histone displacement.

  ~Replacement of octamer subunits with histone variants.
• More in-depth chromatin remodelling.

  ~Histone modification by histone acetyltransferase loosens the attachment of the nucleosome to the DNA.

  ~Remodeling proteins bind, disaggregating the nucleosome.

  ~Now the transcription complex can bind to begin transcription.