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Author Topic:   How, and where, does gene expression work?
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 10 of 12 (170035)
12-20-2004 6:03 AM
Reply to: Message 3 by Ben!
12-13-2004 6:40 PM


Re: (bump!)
Dear Ben,
I'd like to address the specific instance of the SCNT with olfactory cells before addressing the general question of gene expression.
Both the paper by Axel (Eggan, et al., 2004) and a similar paper (Li, et al., 2004) come to the conclusion that there were no genomic rearrangements associated with stable receptor expression. So this is certainly not a case of the SCNT process reversing a rearrangement of the DNA.
As to the general applicability of cloning as a way of testing for irreversible changes to the DNA, this should certainly work in theory but at the moment we don't know enough about the mechanisms involved in 're-setting' nuclei during SCNT to be sure that we arent getting a whole lot of false positives simply because we don't know the right technique to reset that particular change.
A lot of experiments of this type have already been done in otyher systems, some of John Gurdon's very earliest cloning work in amphibians done in the 1960's was on exactly the sort of questions proposed as regards changes during development (Gurdon and Byrne, 2003), as well as a lot of closely related work complementary from the more cloning oriented field as to which cells provide the best source of material and what techniques are best for re-setting them (Gurdon, et al., 2003, Mullins, et al., 2004, Kono, 1997.
As to gene regulation, as has been suggested this is really a very large topic, and we can be pretty certain that we have as yet only a rudimentary grsp of the real complexities involved. As well as the simplest level of regulation, a specific protein binding to a particular DNA site and thereby either promoting or suppressing the expression of the gene by blocking or facilitating the binding of a polymerase there are a host of other possible factors. There are regulatory elements which can function many 100s of Kb upstream of the target gene, some may interact because the DNA conformation brings them into close association but exact mechanisms are still unclear. Factors may alter the DNA structure by the remodelling the histone complement or the methylation or acetylation of histone proteins may lead to a restrictive or permissive environment for gene expression. Changes in the methylation of the DNA can similarly be linked to changes in gene expression, some of which even seem to be heritable cross generationally. The expression of one gene may interfere with another either in the cascading sort of mechanism previously mentioned or in some cases because the transcription of one gene precludes the transcription of another due to their arrangement on the chromosome.
Those are just a few mechanisms related to gene expression that I can think of off the top of my head. As far as your speciifc question of how 1 gene could be stably expressed in preference to 999 others, the most obvious answer is that expression of that one gene acts to supress expression of all the others. It appears that this is probably just a stochastic phenomenon as there seem to some instances where the classes are observed to switch. If you have several million neurons the allowing any cell to find its own class is likely to give you at least some cells expressing each class of receptors, and differences in the proportions of these may well account for different perceptions of smell. I don't know if there is any mechanism for this sort of repression of other receptr genes sadly as I know very little about the organisation of these genes in the genome, if they were all gathered together in one locus then there might be a simpler mechanism than if they were spread all over throughout the genome, a quick check in pubmed tells me that in humans the genes are spread out over 51 loci on 21 chromosomes, so not nicely localised together in that case.
TTFN,
WK

This message is a reply to:
 Message 3 by Ben!, posted 12-13-2004 6:40 PM Ben! has replied

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 Message 11 by Ben!, posted 12-20-2004 5:24 PM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 12 of 12 (170549)
12-21-2004 4:54 PM
Reply to: Message 11 by Ben!
12-20-2004 5:24 PM


Genetic memory
Dear Bencip19,
I can't say for sure but, from what I remember of my undergraduate neurobiology, I think that what he meant is that the mechanism by which long term potentiation is established requires de novo gene expression and protein synthesis while short term potentiation does not.
TTFN,
WK

This message is a reply to:
 Message 11 by Ben!, posted 12-20-2004 5:24 PM Ben! has not replied

  
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