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Promoter


for disambiguation of the term promoter, see the promoter Wiktionary article

In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, which then initiates transcription. In RNA synthesis, promoters are a means to demarcate which genes should be used for messenger RNA creation - and, by extension, control which proteins the cell manufactures.

The perfect promoter is called a canonical sequence.

Contents

Promoter elements

  • Core promoter
    • Transcription Start Site (TSS)
    • Approximately -35
    • A binding site for RNA polymerase
      • RNA-polymerase I: transcribes genes encoding ribosomal RNA
      • RNA-polymerase II: transcribes genes encoding mRNA and certain small nuclear RNAs
      • RNA-polymerase III: transcribes genes encoding tRNAs and other small RNAs
    • General transcription factor binding sites
  • Proximal promoter
    • Approximately -250
    • Specific transcription factor binding sites
  • Distal promoter
    • Anything further upstream (but not an enhancer or other regulatory region whose influence is positional/orientation independent)
    • Specific transcription factor binding sites

Promoters represent critical elements that can work in concert with other regulatory regions (enhancers, silencers, boundary elements /insulators) to direct the level of transcription of a given gene.

Promoter sequences

Prokaryotic promoters

In prokaryotes, the promoter consists of two short sequences at -10 and -35 position upstream of the gene, that is, prior to the gene in the direction of transcription. The sequence at -10 is called the Pribnow box and usually consists of the six nucleotides TATAAT. The Pribnow box is absolutely essential to start transcription in prokaryotes. The other sequence at -35 usually consists of the six nucleotides TTGACA. Its presence allows a very high transcription rate.

   <-- upstream                                                          downstream 
5'-XXXXXXXPPPPPXXXXXXPPPPPPXXXXGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGXXXX-3'
           -35       -10       Gene to be transcribed


Probability of occurrence of each nucleotide

 T    A    T    A    A    T
77%  76%  60%  61%  56%  82%
 T    T    G    A    C    A
69%  79%  61%  56%  54%  54%

Eukaryotic promoters

See Michael Levine and Robert Tjian. "Transcription regulation and animal diversity". Nature 424, 147 - 151 (10 July 2003) [1]

Binding

The binding of a promoter sequence (P) to a sigma factor-RNAP complex (R) is a two step process:

  1. R+P ↔ RP(closed). K = 10E7
  2. RP(closed) RP(open). K = 10E-2

Diseases Associated with Aberrant Promoter Function

Though OMIM is a major resource for gathering information on the relationship between mutations and natural variation in gene sequence and susceptibility to hundreds of diseases, it requires a sophisticated search strategy to extract those diseases that are associated with defects in transcriptional control where the promoter is believed to have direct involvement. This is a list of diseases that evidence suggests have some involvement of promoter malfunction, either through direct mutation of a promoter sequence or mutation in a transcription factor or transcriptional co-activator . Keep in mind that most diseases are heterogenous in etiology, meaning that one "disease" is often many different diseases at the molecular level, though the symptoms exhibited and the response to treatment might be identical. How diseases respond differently to treatment as a result of differences in the underlying molecular origins is partially addressed by the discipline of pharmacogenomics.


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