Previously, I wrote
>Most likely imprinting (much like X chromosome inactivation in females) is a mode of limiting
gene dosage in the cell. Sometimes there can be such a thing as too much of a good thing <grin>!
>
What I ment here and I think is not erroneous is that imprinting can be seen as a means of gene dosage.
I did not say that imprinting and X chromosome are identicle phenomenon....although (<grin>)
There is a gene known as the Xist gene which produces a transcript that may be involved in
silencing the X chromosome (all be it stochastically) and this gene I believe is differentially
methylated....EEEK
There goes Mother nature again throwing a spanner in the works!
Interesting bit on the trinucleotide repeats Jo, hmm maybe there is some sort of choice, as in
classical imprinting, in the early stages of the zygote that determines this... probably like most things
has something to do with accessibility of that region of the genome to proteins that can mark the
DNA by some physical means (methylatio for instance) for latter reference (perhaps something like a
maternally inherited heterochromatin forming protein). I think one mode of expansion of repeats is
slippage of the replication fork and re-initiation of replication. The result it you repeat the same region
twice. It is also interesting that these trinucleotide repeat linked disease have a threshold of repeats
before the disease manifest itself (this is called Anticipation). Why do you suppose that is?
I think recent evidence on the loop like structures of these regions of DNA have shed some light on the
question. At the threshold of repeats they form stem loop like structures which I believe may be very good
replication "blocks" for the advancing polymerase during replication. Following this train of logic... the
polymerase stops/slips and reinitiates causing an expansion in the number of repeats. Now that this
number of repeats is larger you get often methylation of the region (perhaps the expanded region is now a
good target for methylases) and then changes in transcription occur. The regulation of the ajoining gene
is altered, often silencing occurs.....
now this methylation seems awfully reminiscent of imprinting ... which can cause silencing in some loci.
Perhaps this repeats once of sufficient number can trigger a false imprinting at that sight....
Mother Nature again <grin>
Graham
activity.
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Graham Dellaire Snail Mail:
Red Cross, Research
McGill University Montreal Blood Services
Faculty of Medicine 3131 Sherbrooke St. East
Div. of Experimental Medicine Montreal, QC, Canada
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B2XE at musicb.mcgill.ca
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