Promoter

(Redirected from Promoters)
Jump to: navigation, search

WikiDoc Resources for Promoter

Articles

Most recent articles on Promoter

Most cited articles on Promoter

Review articles on Promoter

Articles on Promoter in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Promoter

Images of Promoter

Photos of Promoter

Podcasts & MP3s on Promoter

Videos on Promoter

Evidence Based Medicine

Cochrane Collaboration on Promoter

Bandolier on Promoter

TRIP on Promoter

Clinical Trials

Ongoing Trials on Promoter at Clinical Trials.gov

Trial results on Promoter

Clinical Trials on Promoter at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Promoter

NICE Guidance on Promoter

NHS PRODIGY Guidance

FDA on Promoter

CDC on Promoter

Books

Books on Promoter

News

Promoter in the news

Be alerted to news on Promoter

News trends on Promoter

Commentary

Blogs on Promoter

Definitions

Definitions of Promoter

Patient Resources / Community

Patient resources on Promoter

Discussion groups on Promoter

Patient Handouts on Promoter

Directions to Hospitals Treating Promoter

Risk calculators and risk factors for Promoter

Healthcare Provider Resources

Symptoms of Promoter

Causes & Risk Factors for Promoter

Diagnostic studies for Promoter

Treatment of Promoter

Continuing Medical Education (CME)

CME Programs on Promoter

International

Promoter en Espanol

Promoter en Francais

Business

Promoter in the Marketplace

Patents on Promoter

Experimental / Informatics

List of terms related to Promoter

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Overview

In biology, a promoter is a regulatory region of DNA generally located upstream (towards the 5' region of the anti-sense strand) of a gene that generally promotes transcription of the gene.

The promoter contains specific DNA sequences, response elements, that are recognized by proteins known as transcription factors. These factors bind to the promoter sequences, recruiting RNA polymerase, the enzyme that synthesizes the RNA from the coding region of the gene.

  • In prokaryotes, the promoter is recognized by RNA polymerase and an associated sigma factor, which in turn are brought to the promoter DNA by an activator protein binding to its own DNA sequence nearby.
  • In eukaryotes, the process is more complicated, and at least seven different factors are necessary for the binding of an RNA polymerase II to the promoter.

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.

It is worth noting that promoters are not DNA specific, and can in fact locate upstream towards the 3' end of an RNA genome, e.g. Respiratory Syncytial Virus (RSV).

Identification of relative location

As promoters are typically immediately adjacent to the gene in question, positions in the promoter are designated relative to the transcriptional start site, where transcription of RNA begins for a particular gene (i.e., positions upstream are negative numbers counting back from -1, for example -100 is a position 100 base pairs upstream).

Promoter elements

  • Core promoter - the minimal portion of the promoter required to properly initiate transcription
  • Proximal promoter - the proximal sequence upstream of the gene that tends to contain primary regulatory elements
    • Approximately -250
    • Specific transcription factor binding sites
  • Distal promoter - the distal sequence upstream of the gene that may contain additional regulatory elements, often with a weaker influence than the proximal promoter
    • Anything further upstream (but not an enhancer or other regulatory region whose influence is positional/orientation independent)
    • Specific transcription factor binding sites

Prokaryotic promoters

In prokaryotes, the promoter consists of two short sequences at -10 and -35 positions upstream from the transcription start site. Sigma factors not only help in enhancing RNAP binding to the promoter but helps RNAP target which genes to transcribe.

  • The sequence at -10 is called the Pribnow box, or the -10 element, and usually consists of the six nucleotides TATAAT. The Pribnow box is absolutely essential to start transcription in prokaryotes.
  • The other sequence at -35 (the -35 element) usually consists of the six nucleotides TTGACA. Its presence allows a very high transcription rate.
  • Both of the above consensus sequences, while conserved on average, are not found intact in most promoters. On average only 3 of the 6 base pairs in each consensus sequence is found in any given promoter. No promoter has been identified to date that has intact consensus sequences at both the -10 and -35; it is thought that this would lead to such tight binding by the sigma factor that the polymerase would be unable to initiate productive transcription.
  • Some promoters contain a UP element (consensus sequence 5’-TGNTATAAT-3')upstream of the -35 element; the presence of the -35 element appears to be unimportant for transcription from the UP element-containing promoters.

It should be noted that the above promoter sequences are only recognized by the sigma-70 protein that interacts with the prokaryotic RNA polymerase. Complexes of prokaryotic RNA polymerase with other sigma factors recognize totally different core promoter sequences.

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

(note that the optimal spacing between the -35 and -10 sequences is 17 nt)

Probability of occurrence of each nucleotide

 for -10 sequence
 T    A    T    A    A    T
77%  76%  60%  61%  56%  82%
 for -35 sequence
 T    T    G    A    C    A
69%  79%  61%  56%  54%  54%

Eukaryotic promoters

Eukaryotic promoters are extremely diverse and are difficult to characterize. They typically lie upstream of the gene and can have regulatory elements several kilobases away from the transcriptional start site. In eukaryotes, the transcriptional complex can cause the DNA to bend back on itself, which allows for placement of regulatory sequences far from the actual site of transcription. Many eukaryotic promoters, but by no means all, contain a TATA box (sequence TATAAA), which in turn binds a TATA binding protein which assists in the formation of the RNA polymerase transcriptional complex.[1] The TATA box typically lies very close to the transcriptional start site (often within 50 bases).

Eukaryotic promoter regulatory sequences typically bind proteins called transcription factors which are involved in the formation of the transcriptional complex. An example is the E-box (sequence CACGTG), which binds transcription factors in the basic-helix-loop-helix (bHLH) family (e.g. BMAL1-Clock, cMyc).[2]

Detection of promoters

A wide variety of algorithms have been developed to facilitate detection of promoters in genomic sequence, and promoter prediction is a common element of many gene prediction methods.

Evolutionary change

A major question in evolutionary biology is how important tinkering with promoter sequences is to evolutionary change, for example, the changes that have occurred in the human lineage after separating from chimps.

Some evolutionary biologists, for example Allan Wilson, have proposed that evolution in promoter or regulatory regions may be more important than changes in coding sequences over such time frames.

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 = 107
  2. RP(closed) → RP(open). K = 10−2

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 heterogeneous 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.

Not listed here are the many kinds of cancers that involve aberrant changes in transcriptional regulation owing to the creation of chimeric genes through pathological chromosomal translocation.

Canonical sequences and wild-type

The usage of canonical sequence for a promoter is often problematic, and can lead to misunderstandings about promoter sequences. Canonical implies perfect, in some sense.

In the case of a transcription factor binding site, then there may be a single sequence which binds the protein most strongly under specified cellular conditions. This might be called canonical.

However, natural selection may favor less energetic binding as a way of regulating transcriptional output. In this case, we may call the most common sequence in a population, the wild-type sequence. It may not even be the most advantageous sequence to have under prevailing conditions.

Recent evidence also indicates that several genes (including the proto-oncogene c-myc) have G-quadruplex motifs as potential regulatory signals.

Diseases associated with promoter elements

References

  1. Smale ST, Kadonaga JT (2003). The RNA polymerase II core promoter. Annu Rev Biochem. 72, 449-479. PMID 12651739 PDF
  2. Levine M, Tjian R (2003). Transcription regulation and animal diversity. Nature. 424(6945), 147-151. PMID 12853946 PDF
  3. population genetics study: Hobbs, K.; Negri, J.; Klinnert, M.; Rosenwasser, L.J.; and Borish, L. (1998). Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med. 158 (6), 1958-1962. PMID 9847292
  4. population genetics study: Burchard, E.G.; Silverman, E.K.; Rosenwasser, L.J.; Borish, L.; Yandava, C.; Pillari, A.; Weiss, S.T.; Hasday, J.; Lilly, C.M.; Ford, J.G.; and Drazen, J.M. (1999). Association between a sequence variant in the IL-4 gene promoter and FEV(1) in asthma. Am J Respir Crit Care Med. 160 (3), 919-922. PMID 10471619
  5. Kulozik, A.E.; Bellan-Koch, A.; Bail, S.; Kohne, E.; and Kleihauer, E. (1991). Thalassemia intermedia: moderate reduction of beta globin gene transcriptional activity by a novel mutation of the proximal CACCC promoter element. Blood. 77 (9), 2054-2058. PMID 2018842
  6. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ, et al. (1995). Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 376 (6538), 348-351. PMID 7630403

External links

ar:محفز

da:Promoter (biologi) de:Promotor (Genetik)eo:Promotoroit:Promotore he:קדם nl:Promotor (genetica)sr:Промотер fi:Promoottoriuk:Промотор (біологія) ur:مِعزاز

Cost Effectiveness of Promoter

| group5 = Clinical Trials Involving Promoter | list5 = Ongoing Trials on Promoter at Clinical Trials.govTrial results on PromoterClinical Trials on Promoter at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Promoter | list6 = US National Guidelines Clearinghouse on PromoterNICE Guidance on PromoterNHS PRODIGY GuidanceFDA on PromoterCDC on Promoter


| group7 = Textbook Information on Promoter | list7 = Books and Textbook Information on Promoter


| group8 = Pharmacology Resources on Promoter | list8 = AND (Dose)}} Dosing of PromoterAND (drug interactions)}} Drug interactions with PromoterAND (side effects)}} Side effects of PromoterAND (Allergy)}} Allergic reactions to PromoterAND (overdose)}} Overdose information on PromoterAND (carcinogenicity)}} Carcinogenicity information on PromoterAND (pregnancy)}} Promoter in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Promoter


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Promoter | list9 = AND (pharmacogenomics)}} Genetics of PromoterAND (pharmacogenomics)}} Pharmacogenomics of PromoterAND (proteomics)}} Proteomics of Promoter


| group10 = Newstories on Promoter | list10 = Promoter in the newsBe alerted to news on PromoterNews trends on Promoter</small>


| group11 = Commentary on Promoter | list11 = Blogs on Promoter

| group12 = Patient Resources on Promoter | list12 = Patient resources on PromoterDiscussion groups on PromoterPatient Handouts on PromoterDirections to Hospitals Treating PromoterRisk calculators and risk factors for Promoter


| group13 = Healthcare Provider Resources on Promoter | list13 = Symptoms of PromoterCauses & Risk Factors for PromoterDiagnostic studies for PromoterTreatment of Promoter

| group14 = Continuing Medical Education (CME) Programs on Promoter | list14 = CME Programs on Promoter

| group15 = International Resources on Promoter | list15 = Promoter en EspanolPromoter en Francais

| group16 = Business Resources on Promoter | list16 = Promoter in the MarketplacePatents on Promoter

| group17 = Informatics Resources on Promoter | list17 = List of terms related to Promoter


}}



Linked-in.jpg