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For other uses of this word, see promoter (disambiguation).

In biology, a promoter is a regulatory region of DNA generally located upstream (towards the 5' region of the sense strand) of a gene that generally promotes transcription of the gene. Foundations of modern biology There are five unifying principles Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In molecular biology upstream and downstream both refer to a relative position in DNA or RNA. Directionality, in Molecular biology, refers to the end-to-end chemical orientation of a single strand of Nucleic acid. In Genetics, an antisense strand is the strand of DNA transcribed into MRNA during transcription. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Transcription is the synthesis of RNA under the direction of DNA

Contents

Overview

The promoter contains specific DNA sequences, response elements, that are recognized by proteins known as transcription factors. A response element is a short sequence of DNA within the Promoter of a Gene that is able to bind a specific Hormone receptor complex and therefore In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences These factors bind to the promoter sequences, recruiting RNA polymerase, the enzyme that synthesizes the RNA from the coding region of the gene. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA.

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. In Genetics, an enhancer is a short region of DNA that can be bound with Proteins (namely the Trans-acting factors much like a set of Transcription In Genetics a silencer is a DNA sequence capable of binding transcription regulation factors termed Repressors Upon binding RNA polymerase

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

Prokaryotic promoters

In prokaryotes, the promoter consists of two short sequences at -10 and -35 positions upstream from the transcription start site. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. An impressive 50%+ of all RNA synthesis in a cell is accounted for by the transcription of rRNA Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. RNA polymerase II (also called RNAP II and Pol II) is an enzyme found in eukaryotic cells Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product RNA polymerase III (also called Pol III) transcribes DNA to synthesize ribosomal 5S RRNA, TRNA and other small RNAs Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other Sigma factors not only help in enhancing RNAP binding to the promoter but helps RNAP target which genes to transcribe.

It should be noted that the above promoter sequences are only recognized by the sigma-70 protein that interacts with the prokaryotic RNA polymerase. A sigma factor ( &sigma factor) is a prokaryotic transcription Initiation factor that enables specific binding of RNA polymerase to gene 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    T77%  76%  60%  61%  56%  82%
 for -35 sequence T    T    G    A    C    A69%  79%  61%  56%  54%  54%

Eukaryotic promoters

Eukaryotic promoters are extremely diverse and are difficult to characterize. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex 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. The TATA box (also called Goldberg-Hogness box) is a DNA sequence ( Cis-regulatory element) found in the Promoter region of most genes in The TATA binding protein ( TBP) is a Transcription factor that binds specifically to a DNA sequence called the TATA box. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. [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. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences An example is the E-box (sequence CACGTG), which binds transcription factors in the basic-helix-loop-helix (bHLH) family (e. An E-box is a DNA sequence which usually lies upstream of a Gene in a Promoter region A basic-helix-loop-helix (bHLH is a Protein Structural motif that characterizes a family of Transcription factors. g. BMAL1-Clock, cMyc). Bmal ( brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT-like) is a gene which encodes proteins regulating Circadian rhythm. Myc (cMyc is a gene that regulates other genes It codes for a protein that binds to the DNA of other genes [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. Gene finding typically refers to the area of Computational biology that is concerned with algorithmically identifying stretches of sequence usually genomic DNA

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. Evolutionary biology is a sub-field of Biology concerned with the origin of Species from a Common descent, and Descent of species

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. Allan Charles Wilson ( 18 October 1934 – 21 July 1991) was a pioneer in the use of molecular approaches to understand

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). A sigma factor ( &sigma factor) is a prokaryotic transcription Initiation factor that enables specific binding of RNA polymerase to gene RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. 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. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly

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. Lists of Diseases by name 0-9 A B C D E F G H I J K In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences

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. Pharmacogenomics is the branch of Pharmacology which deals with the influence of genetic variation on drug response in patients by correlating Gene expression

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. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled In Genetics, a chromosome translocation is a Chromosome abnormality caused by rearrangement of parts between nonhomologous Chromosomes.

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. An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. Myc (cMyc is a gene that regulates other genes It codes for a protein that binds to the DNA of other genes Nucleic acid sequences which are rich in Guanine are capable of forming four-stranded structures called G-quadruplexes (Also known as G-tetrads or G4-DNA

Diseases associated with promoter elements

References

  1. ^ Smale ST, Kadonaga JT (2003). Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive Rubinstein-Taybi syndrome (also known as Broad Thumb-Hallux syndrome) is a condition characterized by short stature moderate to severe mental retardation distinctive facial 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

Dictionary

promoter

-noun

  1. One who promotes, particularly with respect to entertainment events or goods.
  2. The section of DNA that controls the initiation of RNA transcription as a product of a gene.
  3. An accelerator of catalysis, though itself is not a catalyst..
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