The TATA-binding protein (TBP) is a
general transcription factor
General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (Promoter (genetics), promoter) on DNA to activate Transcription (genetics), transcription ...
that binds specifically to a
DNA sequence called the
TATA box
In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has ...
. This DNA sequence is found about 30
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s upstream of the
transcription start site
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
in some
eukaryotic
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 ...
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
promoters.
TBP gene family
TBP is a member of a small gene family of TBP-related factors. The first TBP-related factor (TRF/TRF1) was identified in the fruit fly
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
, but appears to be fly or insect-specific. Subsequently
TBPL1
TATA box-binding protein-like protein 1 is a protein that in humans is encoded by the ''TBPL1'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates ...
/TRF2 was found in the genomes of many
metazoa
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
ns, whereas
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
genomes encode a third vertebrate family member,
TBPL2/TRF3. In specific cell types or on specific promoters TBP can be replaced by one of these TBP-related factors, some of which interact with the TATA box similarly to TBP.
Role as transcription factor
TBP is a subunit of the eukaryotic
general transcription factor
General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (Promoter (genetics), promoter) on DNA to activate Transcription (genetics), transcription ...
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 ...
. TFIID is the first protein to bind to DNA during the formation of the
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 ...
of
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 ...
(RNA Pol II).
As one of the few proteins in the preinitiation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the
transcription start site
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
of the gene. However, it is estimated that only 10–20% of human promoters have TATA boxes. Therefore, TBP is probably not the only protein involved in positioning RNA polymerase II. Majority of human promoters are
TATA-less
housekeeping gene
In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions. Although ...
promoters. The binding of TBP to these promoters is facilitated by housekeeping gene regulators.
Interestingly, transcription initiates within a narrow region at around 30 bp downstream of TATA box on TATA-containing promoters, while transcription start sites of TATA-less promoters are dispersed within a 200 bp region.
Binding of TFIID to the
TATA box
In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has ...
in the
promoter region of the gene initiates the recruitment of other factors required for RNA Pol II to begin transcription. Some of the other recruited transcription factors include
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 ...
,
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 pro ...
, and
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 ...
. Each of these transcription factors contains several protein subunits.
TBP is also important for transcription by
RNA polymerase I
RNA polymerase 1 (also known as Pol I) is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA (but not 5S rRNA, which is synthesized by RNA polymerase III), a type of RNA that accounts for over 50% of the total RNA synthesiz ...
and
RNA polymerase III
In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs.
The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose e ...
, and is therefore involved in transcription initiation by all three RNA polymerases.
TBP is involved in
DNA melting
Nucleic acid thermodynamics is the study of how temperature affects the nucleic acid structure of double-stranded DNA (dsDNA). The melting temperature (''Tm'') is defined as the temperature at which half of the DNA strands are in the random coil o ...
(double strand separation) by bending the
DNA by 80° (the AT-rich sequence to which it binds facilitates easy melting). The TBP is an unusual protein in that it binds the minor groove using a β sheet.
Another distinctive feature of TBP is a long string of glutamines in the N-terminus of the protein. This region modulates the DNA binding activity of the C-terminus, and modulation of DNA-binding affects the rate of transcription complex formation and initiation of transcription. Mutations that expand the number of CAG repeats encoding this
polyglutamine tract A polyglutamine tract or polyQ tract is a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units.
A multitude of genes, in various eukaryotic species (including h ...
, and thus increase the length of the polyglutamine string, are associated with
spinocerebellar ataxia
Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of s ...
17, a
neurodegenerative disorder
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
classified as a
polyglutamine disease
Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides ( trinucleotide repeats) inc ...
.
DNA-protein interactions
When TBP binds to a
TATA box
In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has ...
within the
DNA, it distorts the DNA by inserting amino acid side-chains between base pairs, partially unwinding the helix, and doubly kinking it. The distortion is accomplished through a great amount of surface contact between the protein and DNA. TBP binds with the negatively charged phosphates in the DNA backbone through positively charged
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
and
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
amino acid residues. The sharp bend in the DNA is produced through projection of four bulky
phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...
residues into the minor groove. As the DNA bends, its contact with TBP increases, thus enhancing the DNA-protein interaction.
The strain imposed on the DNA through this interaction initiates melting, or separation, of the strands. Because this region of DNA is rich in
adenine
Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...
and
thymine
Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...
residues, which base-pair through only two
hydrogen bonds
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
, the DNA strands are more easily separated. Separation of the two strands exposes the bases and allows
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 ...
to begin transcription of the
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
TBP's C-terminus composes of a helicoidal shape that (incompletely) complements the T-A-T-A region of DNA. This incompleteness allows DNA to be passively bent on binding.
For information on the use of TBP in cells see:
RNA polymerase I
RNA polymerase 1 (also known as Pol I) is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA (but not 5S rRNA, which is synthesized by RNA polymerase III), a type of RNA that accounts for over 50% of the total RNA synthesiz ...
,
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 ...
, and
RNA polymerase III
In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs.
The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose e ...
.
Protein–protein interactions
TATA-binding protein has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
BRF1,
*
BTAF1
TATA-binding protein-associated factor 172 is a protein that in humans is encoded by the ''BTAF1'' gene.
Function
Initiation of transcription by RNA polymerase II requires the assistance of TATA box-binding protein (TBP; MIM 600075) and TBP-as ...
,
* C-Fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...
,
* C-jun
Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...
,
* EDF1
Endothelial differentiation-related factor 1 is a protein that in humans is encoded by the ''EDF1'' gene.
Function
This gene encodes a protein that may regulate endothelial cell differentiation. It has been postulated that the protein function ...
,
* GTF2B
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 pro ...
(TFIIB),
* GTF2A1
Transcription initiation factor IIA subunit 1 is a protein that in humans is encoded by the ''GTF2A1'' gene.
Interactions
GTF2A1 has been shown to interact with TATA binding protein and TBPL1
TATA box-binding protein-like protein 1 is a prot ...
(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 ...
subunit 1),
* GTF2F1
General transcription factor IIF subunit 1 is a protein that in humans is encoded by the ''GTF2F1'' gene.
Interactions
GTF2F1 has been shown to interact with:
* CTDP1,
* GTF2H4,
* HNRPU,
* MED21,
* POLR2A,
* Serum response factor
* TAF1 ...
(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 ...
subunit 1)
* GTF2H4
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the ''GTF2H4'' gene.
Interactions
GTF2H4 has been shown to interact with:
* GTF2F1,
* MED21,
* POLR2A,
* TATA binding protein,
* Transcription Factor II B ...
(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 ...
subunit 4),
* Mdm2,
* MSX1
Homeobox protein MSX-1, is a protein that in humans is encoded by the ''MSX1'' gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue ...
,
* NFYB
Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the ''NFYB'' gene.
Function
The protein encoded by this gene is one subunit of a trimeric complex, forming a highly conserved transcription factor that binds ...
,
* P53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
,[
* ]PAX6
Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene.
Function
PAX6 is a member of the Pax gene family which is responsible for carrying the geneti ...
,
* POLR2A
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that in humans is encoded by the ''POLR2A'' gene.
Function
This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing me ...
,[
* ]POU2F1
POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene.
Interactions
POU2F1 has been shown to interact with:
* EPRS,
* Glucocorticoid receptor,
* Glyceraldehyde 3-phosphate dehydrogenase,
...
,
* RELA
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene.
RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tran ...
,
* NR2B1,
* TAF1
Transcription initiation factor TFIID subunit 1, also known as transcription initiation factor TFIID 250 kDa subunit (TAFII-250) or TBP-associated factor 250 kDa (p250), is a protein that in humans is encoded by the ''TAF1'' gene.
Function
Init ...
,
* TAF4
Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the ''TAF4'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordi ...
,
* TAF5
Transcription initiation factor TFIID subunit 5 is a protein that in humans is encoded by the ''TAF5'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coord ...
,
* TAF6
Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the ''TAF6'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordi ...
,[
* ]TAF7
Transcription initiation factor TFIID subunit 7 also known as TAFII55 is a protein that in humans is encoded by the ''TAF7'' gene.
Function
The intronless gene for this transcription coactivator is located between the protocadherin beta and ga ...
,[
* ]TAF9
TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the ''TAF9'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities ...
.
* TAF10
Transcription initiation factor TFIID subunit 10 is a protein that in humans is encoded by the ''TAF10'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coo ...
,[
* ]TAF11
Transcription initiation factor TFIID subunit 11 also known as TAFII28, is a protein that in humans is encoded by the ''TAF11'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptid ...
,
* TAF13
Transcription initiation factor TFIID subunit 13 is a protein that in humans is encoded by the ''TAF13'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coo ...
, and
* TAF15
TATA-binding protein-associated factor 2N is a protein that in humans is encoded by the ''TAF15'' gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates ...
.
Complex assembly
The TATA-box binding 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 ...
(TBP) is required for the initiation of 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 ...
by RNA polymerases
A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base- ...
I, II and III, from promoters with or without a TATA box. In the presence of a TATA-less promoter, TBP binds with the help of TBP-associated factors (TAFs). TBP associates with a host of factors, including the general 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 TFIIA, -B, -D, -E, and -H, to form huge multi-subunit pre-initiation complexes on the core promoter. Through its association with different 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 ...
factors, TBP can initiate 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 ...
from different RNA polymerase
A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base- ...
s. There are several related TBPs, including TBP-like (TBPL) 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 ...
s.
Structure
The C-terminal core of TBP (~180 residues) is highly conserved
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...
and contains two 88-amino acid repeats that produce a saddle-shaped structure
A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...
that straddles the DNA; this region bind
BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative n ...
s to the TATA box and interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
s with 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 and regulatory
Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. For ...
proteins
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 ...
. By contrast, the N-terminal region varies in both length and sequence
In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...
.
References
External links
GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 17
*
*
*
*
{{DEFAULTSORT:Tata-Binding Protein
Proteins
Genes
Transcription factors