General CpG island questions - (Jun/29/2005 )
Hi,
one other little question
what is this CpG/GpC ratio that is usually refered to. What are the GpCs? and why is that ratio important?
So, do these methylated islands ocurr mostly in silenced genes? and I suppose they are much less common than unmethylated ones? and that all CpG islands associated with active genes are unmethylated?
methylated islands do occur at silenced genes, the best examples are from tumor suppressor genes in cancer, imprinted regions and of course genes found on the X-chromosome and subjected to X-inactivation.
there are hypothesis existing that a demethylase enzyme actively maintains the CpG islands in a hypomethylated state. No one has yet characterised this yet. There are insulator elements such as CTCF and BORIS that bind to hypomethylated GC-rich regions and has been thought to sterically inhibit the methyltransferases from methylating the region.
I think that active transcription of the CpG I assocoiated genes have within the complex, proteins that are refractory to DNMT localisation and thus inhibits methylation.
The underlying question you have asked will be answered by the epigenome project
found here. where every CpG site will be assayed for methylation. At the moment, the models presented by numerous groups are based on the best techniques available for global methylation studies employing methylation sensitive restriction enzymes, it is now becoming clear that MBD proteins are able to bind a single methylated CpG that does not necessarily have to reside in a CpG island, as MBDs are known to be associated with chromatin remodelling proteins and serve a function of maintaining a certain chromatin state, I feel that methylation certaiinly plays a role in chromatin maintenance with "side effects" of regulating gene expression.
Could you forward me the Fyyxel and moon citation? I am unable to find it through a pubmed search.
Cheers
Nick
CpG to GpC ratio is slightly different to the usual calculation of the observed to expected ratio. Obs/exp is a number that is used to determine CpG frequency within a defined sequence. CpG islands also have a large grouping of CpG dinucleotides.
It is known that CpG dinucleotide frequency is five-fold less that what is expected should all dinucleotide combinations be of equal frequency of occurance. There are 16 possible combinations of dinucleotides and if all were equal this would mean a 1/16 expected frequency. Of course what is observed in a sequence is not always what is expected and for regions that are not CpG islands you would see this ratio well below 0.5. However at CpG islands, there are more CpG dinucleotides than expected and the ratio goes above 0.5.
so I hope that explains it a bit more.
Im sorry, but how do you come up with the expected ratio of 0.5?
It is known that CpG dinucleotide frequency is five-fold less that what is expected should all dinucleotide combinations be of equal frequency of occurance. There are 16 possible combinations of dinucleotides and if all were equal this would mean a 1/16 expected frequency. Of course what is observed in a sequence is not always what is expected and for regions that are not CpG islands you would see this ratio well below 0.5. However at CpG islands, there are more CpG dinucleotides than expected and the ratio goes above 0.5.
so I hope that explains it a bit more.
Here is the fomula
CpG obs/exp ratio = CpG observed / CpG expected
= # of CpGs in a windown / [(# of C's)*(# of G's)/Length of window]
it has been arbitrarily determined. this value is a threshold.
anything greater than 0.5 has a higher CG frequency than that expected.
recently a nice review by bird came out in nature, in case someone here is still interested in cpg islands.
Nat Rev Genet. 2008 Jun;9(6):465-76.
DNA methylation landscapes: provocative insights from epigenomics.
Suzuki MM, Bird A.
PMID: 18463664