Talk:Promoter

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Rated "high" as part of gene structure, goes together with exon, intron and terminator (genetics). The article needs references/sources. - tameeria 01:05, 19 February 2007 (UTC)

[edit] upstream/downstream

The introductory section that says it's "is located upstream (towards the 5' region)", I think is wrong. Wouldn't the 3' end be upstream? (RNA polymerase reads 3' --> 5'). —The preceding unsigned comment was added by TriniTriggs (talk • contribs) 19:38, 3 April 2007 (UTC).

Upstream by definition is 5'. Pol II reads 3'-5' on the template strand, which is the complement of the actual gene (the coding strand). When referring to positions on the DNA, you usually go by the coding strand of the gene in question. The promoter is (in every case I've ever seen) on the coding strand. -Cquan (talk, AMA Desk) 20:34, 3 April 2007 (UTC)


This article may be too technical for a general audience.
Please help improve this article by providing more context and better explanations of technical details to make it more accessible, without removing technical details.

Some of the stuff in this article makes no sense at all to somebody without an in-depth understanding of the subject area. E.g. what does all that stuff in the bulleted list mean? JulesH 07:54, 1 October 2006 (UTC)

Wait, if the promoter is +1, and upstream is negative, then how is -100 mean a position 100 bp's upstream from the promoter? To illustrate this point, note how -5 denotes a position 7 bp's upsteam of the promoter: +1 0 -1 -2 -3 -4 -5. I don't have my textbook with me, and I don't have time to search Entrez, but can someone with a good source actually confirm...
The -100 upstream is generally approximate. That is, point mutations can cause a shift. The article is correct; the average position is -100.--Thorwald 02:33, 4 February 2007 (UTC)

No actually when referring to -100 it is not approximate but an exact base pair. Point mutations do not cause a shift in the positions of the sequences, but insertions or deletions of sequences do.--PhDBiochemist 05:57, 4 February 2007 (UTC)

Actually, yes they can. I did not mean a "shift" as in the DNA sequence itself moves anywhere relative to its pre-mutation position. What I meant is something like the following: Assume that the consensus sequence on where a protein will bind is "TTTAA" (I just made that up) and that upstream of this sequence you have something like "nnnnC", where "n" can be any of the four nucleotides. So, the sequence looks like the following:
...nnnncTTTAAnnnn...

where the capital letters are the "recognised" sequences (or binding point) and the small caps are sequences the protein will not bind to. Also assume that this is around 100 bp upstream of the promoter. Now, if _two_ point mutations (not insertions or deletions) occur, one on the 'c' and the other on the third 'T', such that 'c' is mutated into a 'T' and the third 'T' into an 'A' (ignoring, for a moment, that pyrimidines and purines are more likely to remain as such), the new sequence will look like the following:

...nnnnTTTAAAnnnn...

The protein will still recognise the sequence, however, it will now be one bp upstream from its previous position. That is, it will "shift". Of course, this may affect the "viability" of the gene it is turning on or off and it is highly unlikely that two mutations will occur so close to each other during a cell cycle, but it should not change what the protein will bind to. It is possible to think of other sequences that would require only a single mutation to cause that "shift". Any further proteins necessary to complete the "complex" might not be able to bind, but that was not my original point. My point remains that mutation (point, insertion, or deletion) can change the relative position of things and do not, necessarily, mean the gene will be prevented from being transcribed (or, vice verse). Also note that the proteins are not binding to a single nucleotide; usually, three, four, five, or more. So, the "-100" is usually referring to the first (or last or average) position of its consensus sequence.--Thorwald 08:15, 4 February 2007 (UTC)

For more information on how "point mutations" can affect promoters (including the upstream binding positions), see the following references:
  • Chapman KA, Burgess RR (1987). Construction of bacteriophage T7 late promoters with point mutations and characterization by in vitro transcription properties. Nucleic Acids Res 15(13):5413–5432.
  • Price P, et al. (1987). Polymorphisms at positions -22 and -348 in the promoter of the BAT1 gene affect transcription and the binding of nuclear factors. Human Molecular Genetics 13(9):967-974.
  • Pugacheva EM, et al. (2005). Familial cases of point mutations in the XIST promoter reveal a correlation between CTCF binding and pre-emptive choices of X chromosome inactivation. Human Molecular Genetics 14(7):953-965.
  • and many, many more. --Thorwald 10:07, 4 February 2007 (UTC)

You are right to be confused by the nomenclature used. But we don't use the "0" to designate a position. So +1 refers to the actual starting point of transcription and is the first base found in the RNA synthesized by the RNA polyermase (in both prokaryotic and eukaryotic organisms). -1, -2, etc. then refer to DNA base pair positions that are not transcribed and included in the RNA product. In general we have now moved into the promoter region of the gene. Incidentally, the promoter can be defined as the DNA sequences that are required for accurate regulation of transcription. The proximal promoter region (and these have different nomenclatures in prokaryotes and eukaryotes) serves largely as a scaffold to which the protein transcriptional machinery bind and collect to form a complex that subsequently initiates transcription.--PhDBiochemist 16:54, 3 February 2007 (UTC)

  • What is the position of the first bp of the promoter site?
  • What the heck does this mean? "Recent evidence also indicates that several genes (including the proto-oncogene c-myc) have G-quadruplex motifs as potential regulatory signals." I get what a proto-oncogene is, but for god's sake, how does this relate to the sentance before it?

I agree that this needs more explanation, and really g-quadruplex DNA and supercoiling phenomena should be covered separately.--PhDBiochemist 16:54, 3 February 2007 (UTC)

The "G-quadruplex" has to do with four guanines (i.e. "GGGG") that can wrap back or fold on each other to form a structure that appears (roughly) as follows (but think of a "3D" cube):Thorwald 02:33, 4 February 2007 (UTC)
G--G
G--G
N  N
N  N
...

In any case, regulation of transcription by g-quadruplex DNA is at best an obscure idea, and should not be included in this type of article on promoters and how they are regulated. --PhDBiochemist 05:57, 4 February 2007 (UTC)

  • Either link to sigma factors or give a brief explanation here.

In prokaryotes, the sigma factors actually serve to recognize the specific -35 and -10 sequences in the promoter. Roughly, there are now different classes of -35 and -10 sequences to which different sigma factors bind. The sigma factor also forms a complex with RNA polymerase and it is actually this complex that binds to the -35/-10 sequences. In the end, different sigma factors serve to bring the RNA polymerase to these diffent promoters containing different -35/-10 sequences.--PhDBiochemist 16:54, 3 February 2007 (UTC)

  • For the conservation of sequence section, please give 5' and 3' indicators, and please reference a source.
  • Finally, I think I might have heard the term "Canonical sequence" maybe once during all of college. Is it like an EST but derived from genomic DNA and not cDNA? I looked at the stub, but it doesn't seem to totally correspond with the information used in this section.::—Preceding unsigned comment added by 66.240.10.170 (talk)

Canonical sequence refers to the consensus sequence of that particular DNA element. The consensus sequence refers to either a statistical or functional derivation that either statistically indicates what the most common sequence is in a genome or functionally refers to what sequence gives the maximal amount of transcription established by that sequence. For example, the consensus/canonical TATA box sequence is TATAAA. Changing (mutating) the first T to A gives AATAAA, which confers a level of RNA production at only about 20% of that when using TATAAA.--PhDBiochemist 16:54, 3 February 2007 (UTC)

Actually, "canonical sequence" simply means the generally accepted sequence. It can be a "consensus sequence", but does not need to be. That is, a consensus sequence is a sequence that is nearly always (or universally) the same across organisms or, within a given organism's genome, the sequence generally stays the same for multiple genes.--Thorwald 02:33, 4 February 2007 (UTC)

This article seems to be focussing on really obscure aspects of the promoter before its really got a good description of what it does. —Preceding unsigned comment added by 80.42.70.22 (talk)

These are not "obscure aspects" of promoter regions. This is standard molecular and cellular biology. Of course, the article could do a better job at introducing the topic to the layman.--Thorwald 02:33, 4 February 2007 (UTC)

[edit] Promoters and High Salt Content

CAN ANYONE TELL ME ABOUT ANY PROMOTERS ACTIVATED BY HIGH SALT CONTENT...........???????? —Preceding unsigned comment added by 149.155.96.5 (talk) 09:18, 9 October 2007 (UTC)

[edit] sense or antisense

The introduction says

a promoter is a regulatory region of DNA generally located upstream (towards the 5' region of the anti-sense strand)

Shouldn't it be 5' region of sense strand since 5' of anti-sense would mean downstream —Preceding unsigned comment added by 122.162.147.191 (talk) 18:21, 11 May 2008 (UTC)