![Transcription Factors](https://upload.wikimedia.org/wikipedia/commons/8/80/Transcription_Factors.svg)
General transcription factors (GTFs), also known as basal transcriptional factors, are a class of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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. The fu ...
s that bind to specific sites (
promoter) on
DNA to activate
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of genetic information from DNA to
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
. GTFs,
RNA polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template.
Using the enzyme helicase, RNAP locally opens the ...
, and the
mediator
Mediator may refer to:
*A person who engages in mediation
*Business mediator, a mediator in business
* Vanishing mediator, a philosophical concept
* Mediator variable, in statistics
Chemistry and biology
*Mediator (coactivator), a multiprotein ...
(a multi-protein complex) constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription. GTFs are also intimately involved in the process of gene regulation, and most are required for life.
A transcription factor is a protein that binds to specific DNA sequences (
enhancer or promoter), either alone or with other proteins in a complex, to control the rate of transcription of genetic information from DNA to messenger RNA by promoting (serving as an
activator) or blocking (serving as a
repressor
In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...
) the recruitment of RNA polymerase.
As a class of protein, general transcription factors bind to promoters along the DNA sequence or form a large
transcription preinitiation complex
The preinitiation complex (abbreviated PIC) is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transc ...
to activate transcription. General transcription factors are necessary for transcription to occur.
Types
In
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, transcription initiation requires an RNA polymerase and a single GTF:
sigma factor
A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is ho ...
.
![Preinitiation complex](https://upload.wikimedia.org/wikipedia/commons/b/b2/Preinitiation_complex.png)
In
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
and
eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
, transcription initiation requires an RNA polymerase and a set of ''multiple'' GTFs to form a transcription preinitiation complex. The Transcription initiation by eukaryotic
RNA polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryoti ...
involves the following GTFs:
*
TFIIA
Transcription factor TFIIA is a nuclear protein involved in the RNA polymerase II-dependent transcription of DNA. TFIIA is one of several general (basal) transcription factors ( GTFs) that are required for all transcription events that use RNA ...
- Stabilizes the interaction between the TATA box and TFIID/TATA binding protein (TBP)
*
TFIIB
Transcription factor II B (TFIIB) is a general transcription factor that is involved in the formation of the RNA polymerase II preinitiation complex (PIC) and aids in stimulating transcription initiation. TFIIB is localised to the nucleus and pr ...
- recognizes the BRE element in promoters
*
TFIID
Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters o ...
– binds to TBP and recognizes TBP associated factors (TAFs), also adds promoter selectivity
*
TFIIE
Transcription factor II E (TFIIE) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is a tetramer of two alpha and two beta chains and interacts with TAF6/TAFII80, ATF7IP, and varicella ...
- attracts and regulates TFIIH
*
TFIIF
Transcription factor II F (TFIIF) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.
TFIIF is encoded by the , , and genes.
TFIIF binds to RNA polymerase II
RNA polymerase II (RNAP II ...
- Stabilizes RNA polymerase interaction with TBP and TFIIB; helps attract TFIIE and TFIIH
*
TFIIH
Transcription factor II Human (transcription factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 ...
- Unwinds DNA at the transcription start point, phosphorylates Ser5 of the RNA polymerase CCTD, releases RNA polymerase from the promoter
Function and mechanism
In bacteria
A sigma factor is a protein needed only for initiation of
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
synthesis in bacteria. Sigma factors provide promoter recognition specificity to the RNA polymerase (RNAP) and contribute to DNA strand separation, then dissociating from the RNA polymerase core
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
following transcription initiation. The RNA polymerase core associates with the sigma factor to form RNA polymerase holoenzyme. Sigma factor reduces the affinity of RNA polymerase for nonspecific DNA while increasing specificity for promoters, allowing transcription to initiate at correct sites. The core enzyme of RNA polymerase has five subunits (
protein subunits
In structural biology, a protein subunit is a polypeptide chain or single protein molecule that assembles (or "''coassembles''") with others to form a protein complex.
Large assemblies of proteins such as viruses often use a small number of ty ...
) (~400
kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
). Because of the RNA polymerase association with sigma factor, the complete RNA polymerase therefore has 6 subunits: the sigma subunit-in addition to the two alpha (α), one beta (β), one beta prime (β'), and one omega (ω) subunits that make up the core enzyme(~450 kDa). In addition, many bacteria can have multiple alternative σ factors. The level and activity of the alternative σ factors are highly regulated and can vary depending on environmental or developmental signals.
In archaea and eukaryotes
The transcription preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. It attaches to the promoter of the DNA (e.i., TATA box) and helps position the RNA polymerase II to the gene transcription start sites, denatures the DNA, and then starts transcription.
Transcription preinitiation complex assembly
The assembly of transcription preinitiation complex follows these steps:
#
TATA binding protein
The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene p ...
(TBP), a subunit of TFIID (the largest GTF) binds to the promoter (TATA box), creating a sharp bend in the promoter DNA. Then the TBP-TFIIA interactions recruit TFIIA to the promoter.
# TBP-TFIIB interactions recruit TFIIB to the promoter. RNA polymerase II and TFIIF assemble to form the Polymerase II complex. TFIIB helps the Pol II complex bind correctly.
# TFIIE and TFIIH then bind to the complex and form the transcription preinitiation complex. TFIIA/B/E/H leave once RNA elongation begins. TFIID will stay until elongation is finished.
# Subunits within TFIIH that have
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
and
helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
activity create negative superhelical tension in the DNA. This negative superhelical tension causes approximately one turn of DNA to unwind and form the transcription bubble.
# The template strand of the transcription bubble engages with the RNA polymerase II active site, then RNA synthesis starts.
References
External links
*
Holoenzymesat the US National Library of Medicine Medical Subject Headings
DNA Transcription YouTube Video
{{DEFAULTSORT:General Transcription Factor
Transcription factors