Download bio-of-cells-lent-essay-plan-dna-packaging-in

BOC Essay Plan
How do eukaryotes package their DNA into the nucleus?
Introduction
DNA wrapped around histones forms chromatin
more than 2 meters of DNA in each nucleus => packed into 10 micrometer of
nucleus by packaging using histones to form nucleosomes, and using scaffolding
proteins to create the larger scale structure of the chromosomes.
Nucleosome structure a nucleosome is the smallest unit of chromatin, made up of DNA wrapped
around 8 histones.
 Histones are strongly positively charged due to their high number of
Arginine and Lysine amino acid residues,
 And so are attracted to and negatively charged DNA, with the negative
charge from the phosphate groups in phosphodiester backbone.
 The octameric histone core contains two copies of H2a, H2b, H3 and H4
each, around which roughly 200bp of DNA is tightly wrapped.
 Evidence for the amount of DNA in each nucleosome, that helped with
determination of their structure, comes from an experiment in which
DNAse enzymes were used to carry out partial digests of the chromatin.
The DNAse enzymes cannot hydrolyse DNA that is wound around
histones, although it can cleave DNA between them. Gel electrophoresis of
the DNA from these partial digests suggests that 200 base pairs are in
each nucleosome, as the fragments increased in size in 200bp steps.
 Histone H1 is not a part of the octameric core, and instead acts as a clamp
to keep the nucleosome together.
 Nucleosomes resemble ‘beads on a string’, and are involved in further
interactions to condense the DNA.


The larger scale compaction of DNA in chromsomes involves long range
interactions and the presence of scaffold proteins.
- chromatin packaging forms higher order structure in 30nm fibre.
These form even higher order structure around scaffold proteins,
such as Condensin I and II, that attach to AT rich regions of the
DNA. The results of expeiments on amphibian oocytes have
suggested that the overall stability and structure of condensed
chromatin and condensation of different chromsomes required the
function of topoisomersase enzymes and these scaffold proteins.
However the mechaniscs of compaction from 30nm chromatin fibres to
highly condensed sections of chromosomes is not well understood.
Chromatin can be more tightly or less tightly packed, which is involved in
controlling the level of gene expression in different regions of the chromosomes.
 Nucleosomes not evenly distributed in chromosomes, and the level of
condensing in different regions of the same chromosomes as well as


between different chromomsomes is variable- - e.g. Promoter regions –
devoid of nucleosomes to give access to transcription factors. x
chromosomes.
Chromatin remodelling, changing the level of compaction and density of
nucleosomes, is a mechanism of regulating gene expression, as in order
for transcription to occur RNA polymerase must be able to access and
bind to the DNA.
Post translational Modifications of histone tails, chains of protein
extending from the histones in the core of the nucleosome, affect level of
compaction and therefore level of gene expression. One form of histone
modification associated with increased levels of transcription is
acetylation of particular lysine residues on the histone tails, as carried out
by histone acetyltransferase enzymes. The result of this a region of DNA
with fewer nucleosomes, more widely spread apart and accessible to RNA
polymerase, while deacetlyation of the lysine residues by histone
deacetyltransferase enzymes results in a greater level of compaction.
Conclusion