[Bioperl-l] GeneStructure & Promoter(s)

[Samuel Aparicio]

"Osborne, Brian" wrote:

> Bioperl,
>
> >>A
> > > related question is then also what distinguishes promoters() from
> > > regulatory_elements().
>
> Ask 10 molecular biologists a question, get 10 different answers. But on
> this point I'd guess 7 out of 10 biologists would agree that a promoter is
> that region of the gene 5' to the start codon that's necessary for
> transcriptional initiation. This region usually contains the TATA consensus
> (TATA box). It is typically separated from regulatory elements, which are
> usually more 5'. There will be exceptions. A regulatory element may be
> positive (e.g. enhancer, UAS) or negative (e.g. URS, repressor binding
> site).
>
> These distinctions are not arbitrary, but based on the precise dissection of
> the 5' region. For example, one might remove a UAS and render the gene
> uninducible, but still transcribed. But if one removes the promoter the gene
> can't be transcribed, irrespective of the UAS. These sorts of studies
> indicated that the promoter is a binding site for RNA polymerase and
> associated initiation factors, and positive regulatory elements are not.
> These inferences were later proven by in vitro biochemistry.
>
> There are situations where a gene has multiple start sites of transcription,
> and these can be explained by multiple promoters or TATA boxes, in mammalian
> cells in particular (in yeast there can be multiple start sites and a single
> promoter). These start sites could be used in different biological
> conditions, thus they are regulated, giving rise to one the exceptions I
> mentioned. The regulatory elements and the promoter may be so interdigitated
> in these situations that they cannot be mutated independently - it may be
> difficult to tell whether they overlap or are the same.
>
> There was also a question about regulatory elements and transcripts. There
> are a number of well known cases of such elements in transcribed regions.
> One of the most famous, perhaps one of the first, is the immunoglobulin
> "heavy chain*" enhancer in its first intron. So this DNA element is a
> classic transcriptional enhancer.
>
> Regulatory regions have also been found in the transcribed 3' ends of genes,
> and the problem for you here is that this regulation may be transcriptional
> or post-transcriptional. For example, the iron regulatory element (IRE) of
> the mammalian ferritin mRNA regulates the stability of the mRNA - more iron
> and the mRNA is more stable, and this depends on the regulatory sequence in
> the mRNA. Biologists consider these RNA elements to be true regulatory
> elements, though they are not that common.
>
> I apologize if I've been too didactic.

I agree with everything you say, however I would still argue that the
biochemical
definition of a promoter (as the site where RNApol binds and initiates
transcription)
is more usefully considered as some subset of elements which govern gene
transcription.
Although this is not semantically correct, from the point of view of a gene
locus sequence
it allows one to consider all of the elements which determine transcription
under
one placeholder. As you say, the classical use of the term promoter would only
include RNApol sites, but many people have dissected "promoters" as RNApolII
sites with associated nearby transcription factor binding sites which act
directly
in a complex with RNApol to allow transcription and refer to this complex as a
promoter.
This suggests that the use of the term promoter has in any case become
corrupted.

I would vote for the scheme suggested by Elia in an earlier posting - it seems
that would
be an extensible container under which all kinds of elements with putative
effects
on transcription could be included at a later date. The proposal also separates
out
the RNApol site (TATA or similar) from adjunct elements which interact directly

with RNApol. To keep closer to the strict definition
of promoter I suppose one could call the container
TranscriptionControlElementI?

Cheers
Sam
--
Dr Samuel Aparicio BMBCh PhD | saparici@hgmp.mrc.ac.uk
Wellcome Trust Centre for Molecular Mechanisms in Disease
Cambridge CB2 2XY. UK. | +44 1223 762663 (tel)