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Transcription factor

In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence.[1][2] The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome.[3][4][5] Transcription factors are members of the proteome as well as regulome.

TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes.[6][7][8]


A defining feature of TFs is that they contain at least one DNA-binding domain (DBD), which attaches to a specific sequence of DNA adjacent to the genes that they regulate.[9][10] TFs are grouped into classes based on their DBDs.[11][12] Other proteins such as coactivators, chromatin remodelers, histone acetyltransferases, histone deacetylases, kinases, and methylases are also essential to gene regulation, but lack DNA-binding domains, and therefore are not TFs.[13]


TFs are of interest in medicine because TF mutations can cause specific diseases, and medications can be potentially targeted toward them.

stabilize or block the binding of RNA polymerase to DNA

[17]

recruit or corepressor proteins to the transcription factor DNA complex[18]

coactivator

Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate. Depending on the transcription factor, the transcription of the adjacent gene is either up- or down-regulated. Transcription factors use a variety of mechanisms for the regulation of gene expression.[16] These mechanisms include:

binding – Not only is ligand binding able to influence where a transcription factor is located within a cell but ligand binding can also affect whether the transcription factor is in an active state and capable of binding DNA or other cofactors (see, for example, nuclear receptors).

ligand

[41][42] – Many transcription factors such as STAT proteins must be phosphorylated before they can bind DNA.

phosphorylation

interaction with other transcription factors (e.g., homo- or hetero-) or coregulatory proteins

dimerization

(DBD), which attaches to specific sequences of DNA (enhancer or promoter. Necessary component for all vectors. Used to drive transcription of the vector's transgene promoter sequences) adjacent to regulated genes. DNA sequences that bind transcription factors are often referred to as response elements.

DNA-binding domain

(AD), which contains binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activation functions (AFs), Transactivation domain (TAD) or Trans-activating domain TAD, not to be confused with topologically associating domain (TAD).[53]

Activation domain

An optional signal-sensing domain (SSD) (e.g., a ligand-binding domain), which senses external signals and, in response, transmits these signals to the rest of the transcription complex, resulting in up- or down-regulation of gene expression. Also, the DBD and signal-sensing domains may reside on separate proteins that associate within the transcription complex to regulate gene expression.

Role in biocontrol activity[edit]

The transcription factors have a role in resistance activity which is important for successful biocontrol activity. The resistant to oxidative stress and alkaline pH sensing were contributed from the transcription factor Yap1 and Rim101 of the Papiliotrema terrestris LS28 as molecular tools revealed an understanding of the genetic mechanisms underlying the biocontrol activity which supports disease management programs based on biological and integrated control.[86]

Analysis[edit]

There are different technologies available to analyze transcription factors. On the genomic level, DNA-sequencing and database research are commonly used.[87] The protein version of the transcription factor is detectable by using specific antibodies. The sample is detected on a western blot. By using electrophoretic mobility shift assay (EMSA),[88] the activation profile of transcription factors can be detected. A multiplex approach for activation profiling is a TF chip system where several different transcription factors can be detected in parallel.


The most commonly used method for identifying transcription factor binding sites is chromatin immunoprecipitation (ChIP).[89] This technique relies on chemical fixation of chromatin with formaldehyde, followed by co-precipitation of DNA and the transcription factor of interest using an antibody that specifically targets that protein. The DNA sequences can then be identified by microarray or high-throughput sequencing (ChIP-seq) to determine transcription factor binding sites. If no antibody is available for the protein of interest, DamID may be a convenient alternative.[90]

are involved in the formation of a preinitiation complex. The most common are abbreviated as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. They are ubiquitous and interact with the core promoter region surrounding the transcription start site(s) of all class II genes.[91]

General transcription factors

Upstream transcription factors are proteins that bind somewhere upstream of the initiation site to stimulate or repress transcription. These are roughly synonymous with specific transcription factors, because they vary considerably depending on what are present in the proximity of the gene.[92]

recognition sequences

-- a metadatabase of multiple databases, including JASPAR and others

footprintDB

: database of transcription factor binding sites for eukaryotes

JASPAR

: Plant transcription factor database[95]

PlantTFD

: Database of transcription co-factors and transcription factor interactions[96]

TcoF-DB

: database of human, mouse and rat TF candidates

TFcheckpoint

(now commercial, selling reagents)

transcriptionfactor.org

: An integrative cell-specific database of transcription factor binding motifs coupled with DNA methylation profiles. [97]

MethMotif.org

There are numerous databases cataloging information about transcription factors, but their scope and utility vary dramatically. Some may contain only information about the actual proteins, some about their binding sites, or about their target genes. Examples include the following:

at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Transcription+Factors

Archived 4 December 2008 at the Wayback Machine

Transcription factor database