In the field of molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor) is a protein that binds to specific parts of DNA using DNA binding domains and is part of the system that controls the transfer (or transcription) of genetic information from DNA to RNA. Molecular biology is the study of Biology at a molecular level Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known A DNA-binding domain (DBD includes any protein motif that binds to double- or single-stranded DNA with affinity to a specific sequence or set thereof or a general Transcription is the synthesis of RNA under the direction of DNA Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units ^[1][2]

Transcription factors perform this function alone, or by using other proteins in a complex, by increasing (as an activator), or preventing (as a repressor) the presence of RNA polymerase, the enzyme which activates the transcription of genetic information from DNA to RNA. An activator is a DNA-binding protein that regulates one or more Genes by increasing the rate of transcription. For other uses see Repression A repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. Transcription is the synthesis of RNA under the direction of DNA ^[3][4][5]

Biological roles

The transcription factor TATA binding protein (blue) bound to DNA (red). Transcription is the synthesis of RNA under the direction of DNA Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product Gene modulation redirects here For information on therapeutic regulation of gene expression see Therapeutic gene modulation. WikipediaWikipedia is not a dictionary ---> Downregulation is the process by which WikipediaWikipedia is not a dictionary ---> Downregulation is the process by which A coactivator is a protein that increases Gene expression by binding to an activator (or Transcription factor) which contains a DNA binding domain A corepressor is a protein that decreases Gene expression by binding to a Transcription factor which contains a DNA binding domain. The TATA binding protein ( TBP) is a Transcription factor that binds specifically to a DNA sequence called the TATA box. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Image by David S. Goodsell based on the crystal structure 1cdw from the Protein Data Bank. Proteins are an important class of biological Macromolecules present in all biological organisms made up of such elements as Carbon, Hydrogen

Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes. Below are some of the important functions and biological roles transcription factors are involved in:

• Basal transcription regulation In eukaryotes, an important class of transcription factors called general transcription factors (GTFs) are necessary for transcription to occur. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex General transcription factors (GTF's or basal transcription factors are Protein Transcription factors that have been shown to be important in the Many of these GTFs don't actually bind DNA but are part of the large transcription preinitiation complex that interacts with RNA polymerase directly. The preinitiation complex (abbreviated PIC) is a large complex of Proteins that is necessary for the transcription of protein-coding Genes in RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. The most common GTFs are TFIIA, TFIIB, TFIID (see also TATA binding protein), TFIIE, TFIIF, and TFIIH. Transcription factor TFIIA is a nuclear Protein involved in the RNA polymerase II -dependent transcription of DNA. Transcription Factor II B (TFIIB is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex. Transcription Factor II D (TFIID is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex. The TATA binding protein ( TBP) is a Transcription factor that binds specifically to a DNA sequence called the TATA box. Transcription Factor II E (TFIIE is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex Transcription Factor II F (TFIIF is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex Transcription Factor II H ( TFIIH) is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex.

• Development Many transcription factors in multicellular organisms are involved in development. Multicellular organisms are Organisms consisting of more than one cell, and having Differentiated cells that perform specialized functions Responding to cues (stimuli), these transcription factors turn on/off the transcription of the appropriate genes which in turn allows for changes in cell morphology or activities needed for cell fate determination and cellular differentiation. The term morphology in Biology refers to the outward appearance ( Shape, Structure, Colour, Pattern) of an Organism Cell fate determination is the programming of a cell to follow a specified path of Cell differentiation. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. The Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans. Homeotic genes specify the anterior-posterior axis and segment identity In the field of Developmental biology, regional specification is the process by which different areas are identified in the development of the early Embryo. Another example is the transcription factor encoded by the Sex-determining Region Y (SRY) gene which plays a major role in determining gender in humans. SRY ( Sex-determining Region Y) is a Sex -determining Gene on the Y chromosome in the Therians (placental mammals and marsupials

• Response to intercellular signals Cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another If the signal requires upregulation or downregulation of genes in the recipient cell, often transcription factors will be downstream in the signaling cascade. Estrogen signaling is an example of a fairly short signaling cascade that involves the estrogen receptor transcription factor: estrogen is secreted by tissues such as the ovaries and placenta, crosses the cell membrane of the recipient cell, and is bound by the estrogen receptor in the cell's cytoplasm. Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, The estrogen receptor (ER is a member of the nuclear hormone family of Intracellular receptors which is activated by the Hormone 17β-estradiol "Ovaria" redirects here This is also a proposed section and a Synonym of Solanum. The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. The estrogen receptor then goes to the cell's nucleus and binds to its DNA binding sites, changing the transcriptional regulation of the associated genes.

• Response to environment Not only do transcription factors act downstream of signaling cascades related to biological stimuli, but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF) which upregulates genes necessary for survival at higher temperatures, hypoxia inducible factor (HIF) which upregulates genes necessary for cell survival in low oxygen environments, and sterol regulatory element binding protein (SREBP) which helps maintain proper lipid levels in the cell. Heat shock factor (HSF in Molecular biology, is the name given to Transcription factors that regulate the expression of the Heat shock proteins. Hypoxia-inducible factors (HIFs are Transcription factors that respond to changes in available Oxygen in the cellular environment in specific to decreases in oxygen Sterol Regulatory Element Binding Protein s ( SREBP s are Transcription factors that bind to the Sterol regulatory element DNA sequence Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble

• Cell cycle control Many transcription factors, especially some that are oncogenes or tumor suppressors, help regulate the cell cycle and as such determine how large a cell will get and when it can divide into two daughter cells. An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer One example is the Myc oncogene, which has important roles in cell growth and apoptosis. Myc (cMyc is a gene that regulates other genes It codes for a protein that binds to the DNA of other genes The term cell growth is used in two different ways in Biology.

Regulation of transcription factor activity

It is common in biology for important processes to have multiple layers of regulation and control. This is just as true with transcription: not only do rates of transcription regulate the amounts of gene products (RNA and protein) available to the cell, but the process of transcription itself is regulated. Below is a brief synopsis of some of the ways that the activity of transcription factors can be regulated:

• Transcription factor synthesis Transcription factors (like all proteins) are transcribed from a gene on a chromosome into RNA, and then the RNA is translated into protein. Any of these steps can be regulated to affect the production (and thus activity) of a transcription factor. One interesting implication of this is that transcription factors can regulate themselves. For example, in a negative feedback loop, the transcription factor acts as its own repressor: if the transcription factor protein binds the DNA of its own gene, it will down-regulate the production of more of itself. This is one mechanism to maintain low levels of a transcription factor in a cell.

• Localization to the nucleus In eukaryotes, transcription factors (like most proteins) are transcribed in the nucleus but are then translated in the cell's cytoplasm. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Many proteins that are active in the nucleus contain nuclear localization signals that direct them to the nucleus. A nuclear localizing sequence ( NLS) is an Amino acid sequence which acts like a 'tag' on the exposed surface of a Protein. But for many transcription factors this is a key point in their regulation. Important classes of transcription factors such as some nuclear receptors must first bind a ligand while in the cytoplasm before they can relocate to the nucleus. In the field of Molecular biology, nuclear receptors are a class of Proteins found within the interior of cells that are responsible for sensing the presence of In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally

• Activation via chemical modifications or ligand binding Not only is ligand binding able to influence where a transcription factor is located within a cell, but this can also affect whether the transcription factor is in an active state and capable of binding DNA or other cofactors. Another way that a transcription factor can be activated is by chemical modification of the transcription factor itself. For example, many transcription factors such as STAT proteins must be phosphorylated before they can bind DNA. The Signal Transducers and Activator of Transcription (STAT also called signal transduction and transcription protein s regulate many aspects of Cell growth, survival and Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule

• Accessibility of DNA binding site In eukaryotes, genes that are not being actively transcribed are often located in heterochromatin. Heterochromatin is a tightly packed form of DNA Its major characteristic is that transcription is limited Heterochromatin are regions of chromosomes that are heavily compacted by tightly bundling the DNA onto histones and then organizing the histones into compact chromatin fibers. In Biology, histones are the chief Protein components of Chromatin. Chromatin is the complex basis of DNA and protein that makes up Chromosomes It is found inside the nuclei of eukaryotic cells, and within the DNA within heterochromatin is inaccessible to many transcription factors. For the transcription factor to bind to its DNA binding site the heterochromatin must be first converted to euchromatin, usually via histone modifications. Euchromatin is a lightly packed form of Chromatin that is rich in Gene concentration and is often (but not always under active transcription. The packaging of the Eukaryotic Genome into highly condensed Chromatin makes it inaccessible to the factors required for gene Transcription, DNA replication A transcription factor's DNA binding site may also be inaccessible if the site is already occupied by another transcription factor. Pairs of transcription factors can play antagonistic roles (activator versus repressor) in the regulation of the same gene.

• Availability of other cofactors/transcription factors needed for a complex Most transcription factors don't work alone. Often for gene transcription to occur, a number of transcription factors must bind to DNA regulatory sequences. This collection of transcription factors in turn recruit intermediary proteins such as cofactors that allow efficient recruitment of the preinitiation complex and RNA polymerase. In the field of Molecular biology, transcription coregulators are Proteins that interact with Transcription factors to either activate or repress the The preinitiation complex (abbreviated PIC) is a large complex of Proteins that is necessary for the transcription of protein-coding Genes in RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. Thus, for a single transcription factor to initiate transcription, all of these other proteins must also be present and the transcription factor must be in a state where it can bind to them if necessary.

Structure

Schematic diagram of the amino acid sequence (amino terminus to the left and carboxylic acid terminus to the right) of a prototypical transcription factor which contains (1) a DNA-binding domain (DBD), (2) signal sensing domain (SSD), and a transactivation domain (TAD). The order of placement and the number of domains may differ in various types of transcription factors. In addition, the transactivation and signal sensing functions are frequently contained within the same domain.

Transcription factors are modular in structure and contain the following domains:^[1]

• DNA-binding domain (DBD) which attach to specific sequences of DNA (enhancer or promoter sequences) adjacent to regulated genes. A protein domain is a part of protein sequence and structure that can evolve, function and exist independently of the rest of the protein chain A DNA-binding domain (DBD includes any protein motif that binds to double- or single-stranded DNA with affinity to a specific sequence or set thereof or a general 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 Biology, a promoter is a region of DNA that facilitates the transcription of a particular Gene. DNA sequences which bind transcription factors are often referred to as response elements. A hormone response element (HRE is a Response element for Hormones, a short sequence of DNA within the Promoter of a gene that is able to bind
• Trans-activating domain (TAD) which contain binding sites for other proteins such as transcription coregulators. In the field of Molecular biology, transcription coregulators are Proteins that interact with Transcription factors to either activate or repress the These binding sites are frequently referred to as activation functions (AFs). ^[6]
• An optional signal sensing domain (SSD) (e. g. , a ligand binding domain) which senses external signals and in response transmit these signals to the rest of the transcription complex resulting in up or down regulation of gene expression. Alternatively the DBD and signal sensing domains may reside on separate proteins that associate within the transcription complex to regulate gene expression.

DNA binding domain

Main article: DNA binding domain

The portion (domain) of the transcription factor that binds DNA is called its DNA binding domain. A DNA-binding domain (DBD includes any protein motif that binds to double- or single-stranded DNA with affinity to a specific sequence or set thereof or a general A protein domain is a part of protein sequence and structure that can evolve, function and exist independently of the rest of the protein chain Below is a partial list of some of the major families of DNA-binding domains/transcription factors:

• lambda repressor-like (SCOP 47413) (IPR010982)
• C-terminal effector domain of the bipartite response regulators (SCOP 46894) (IPR001789)
• srf-like (serum response factor) (SCOP 55455) (IPR002100)
• basic-helix-loop-helix (SCOP 47460) (IPR001092)
• GCC box (SCOP 54175)
• Zn₂/Cys₆ (SCOP 57701)
• winged helix (SCOP 46785) (IPR011991)
• Zn₂/Cys₈ nuclear receptor zinc finger (SCOP 57716) (IPR001628)
• homeodomain proteins - bind to homeobox DNA sequences which in turn encode other transcription factors. Enterobacteria phage λ ( Lambda phage) is a temperate bacteriophage that infects Escherichia coli The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid A basic-helix-loop-helix (bHLH is a Protein Structural motif that characterizes a family of Transcription factors. The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid Consisting of about 110 Amino acids, the domain in winged-helix transcription factors has four helices and a two-strand Beta-sheet. The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid In the field of Molecular biology, nuclear receptors are a class of Proteins found within the interior of cells that are responsible for sensing the presence of The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The homeodomain fold is a Protein Structural domain that binds DNA or RNA and is thus commonly found in Transcription factors The A homeobox is a DNA sequence found within Genes that are involved in the regulation of patterns of development ( Morphogenesis) in Animals Homeodomain proteins play critical roles in the regulation of development. Developmental Biology is the official journal of the Society for Developmental Biology. (SCOP 46689) (IPR009057)
• multi-domain Cys₂His₂ zinc fingers (SCOP 57667) (IPR007087)
• basic-leucine zipper (bZIP) (SCOP 57959) (IPR004827)

There are other proteins that play crucial roles in the regulation of transcription, that aren't classified as transcription factors because they lack DNA binding domains. The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid The Structural Classification of Proteins (SCOP database is a largely manual classification of protein Structural domains based on similarities of their Amino acid A DNA-binding domain (DBD includes any protein motif that binds to double- or single-stranded DNA with affinity to a specific sequence or set thereof or a general ^[7] (for example coactivators, chromatin remodelers, histone acetylases, deacetylases, kinases, and methylases). A coactivator is a protein that increases Gene expression by binding to an activator (or Transcription factor) which contains a DNA binding domain RSC is a 15- Subunit complex with the capacity to remodel the structure of Chromatin. Histone acetyltransferases (HAT are Enzymes that acetylate conserved Lysine Amino acids on Histone proteins by transferring an Histone deacetylases (HDAC ( EC number 351 are a class of Enzymes that remove Acetyl groups from an ε-N-acetyl Lysine Amino acid In Chemistry and Biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of Enzyme that transfers Phosphate A methylase is an Enzyme that attaches a Methyl group to a Molecule.

Transcription factor binding sites/response elements

The DNA sequence that a transcription factor binds to is called a transcription factor binding site or response element.

Chemically, transcription factors usually interact with their binding sites using a combination of hydrogen bonds and Van der Waals forces. A hydrogen bond results from a Dipole-dipole force between an Electronegative atom and a Hydrogen atom bonded to Nitrogen, Oxygen The Van der Waals equation is an Equation of state that can be derived from a special form of the potential between a pair of molecules (hard-sphere repulsion Due to the nature of these chemical interactions, most transcription factors bind DNA in a sequence specific manner. However, not all bases in the transcription factor binding site may actually interact with the transcription factor. In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called In addition some of these interactions may be weaker than others. Thus, transcription factors don't bind just one sequence but are capable of binding a subset of closely related sequences, each with a different strength of interaction.

For example, although the consensus binding site for the TATA binding protein (TBP) is:

TATAAAA

the TBP transcription factor can also bind similar sequences such as:

TATATAT or TATATAA

Because transcription factors can bind a set of related sequences and the sequences don't tend to be that long, potential transcription factor binding sites can occur just by chance if the DNA sequence is long enough. In Molecular biology and Bioinformatics, a consensus sequence is a way of representing the results of a multiple Sequence alignment, where related sequences The TATA binding protein ( TBP) is a Transcription factor that binds specifically to a DNA sequence called the TATA box. It is unlikely, however, that a transcription factor binds all compatible sequences in the genome of the cell. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Other constraints, such as DNA accessibility in the cell or availability of cofactors may also help dictate where a transcription factor will actually bind. Thus, given the genome sequence it is still difficult to predict where a transcription factor will actually bind in a living cell.

Classes

Mechanistic

There are three mechanistic classes of transcription factors:

• General transcription factors are involved in the formation of a preinitiation complex. General transcription factors (GTF's or basal transcription factors are Protein Transcription factors that have been shown to be important in the The preinitiation complex (abbreviated PIC) is a large complex of Proteins that is necessary for the transcription of protein-coding Genes in The most common are abbreviated as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. Transcription factor TFIIA is a nuclear Protein involved in the RNA polymerase II -dependent transcription of DNA. Transcription Factor II B (TFIIB is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex. Transcription Factor II D (TFIID is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex. Transcription Factor II E (TFIIE is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex Transcription Factor II F (TFIIF is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex Transcription Factor II H ( TFIIH) is one of several General transcription factors that make up the RNA polymerase II Preinitiation complex. They are ubiquitous and interact with the core promoter region surrounding the transcription start site(s) of all class II genes. A class II gene is a type of Gene that codes for a Protein. Class II genes are transcribed by RNAP II. ^[8]
• Upstream transcription factors are proteins that bind somewhere upstream of the initiation site to stimulate or repress transcription.
• Inducible transcription factors are similar to upstream transcription factors but require activation or inhibition.

Functional

Transcription factors have been classified according to their regulatory function:^[7]

• I. constitutively-active - present in all cells at all times - general transcription factors, Sp1, NF1, CCAAT
• II. General transcription factors (GTF's or basal transcription factors are Protein Transcription factors that have been shown to be important in the See also SP1. Sp1 is a human Transcription factor involved in gene expression in the early development of an organism CCAAT-enhancer-binding proteins (or C/EBPs are a family of Transcription factors that are composed of six members C/EBP α to C/EBP ζ conditionally-active - requires activation
  • II. A developmental (cell specific) - expression is tightly controlled, but, once expressed, require no additional activation - GATA, HNF, PIT-1, MyoD, Myf5, Hox, Winged Helix
  • II. GATA transcription factor s are a family of Transcription factors characterized by their ability to bind to the sequence "GATA" Hepatocyte nuclear factors (HNFs are a group of phylogenetically unrelated Transcription factors that regulate the Transcription of a diverse group of Genes POU domain class 1 transcription factor 1 (Pit1 growth hormone factor 1, also known as POU1F1, is a Transcription factor for Growth hormone. MyoD is a Protein with a key role in regulating Muscle Myf5 is a Protein with a key role in regulating Muscle differentiation. Homeotic genes specify the anterior-posterior axis and segment identity Consisting of about 110 Amino acids, the domain in winged-helix transcription factors has four helices and a two-strand Beta-sheet. B signal-dependent - requires external signal for activation
    • II. B. 1 extracellular ligand-dependent - nuclear receptors
    • II. In the field of Molecular biology, nuclear receptors are a class of Proteins found within the interior of cells that are responsible for sensing the presence of B. 2 intracellular ligand-dependent - activated by small intracellular molecules - SREBP, p53, orphan nuclear receptors
    • II. Sterol Regulatory Element Binding Protein s ( SREBP s are Transcription factors that bind to the Sterol regulatory element DNA sequence p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene B. 3 cell membrane receptor-dependent- second messenger signaling cascades resulting in the phosphorylation of the transcription factor
      • II. B. 3. a resident nuclear factors - reside in the nucleus regardless of activation state - CREB, AP-1, Mef2
      • II. CREB ( cAMP response element-binding Proteins are Transcription factors which bind to certain DNA sequences called CAMP response In the field of Molecular biology, myocyte enhancer factor-2 ( Mef2) Proteins are a family of Transcription factors which through control of B. 3. b latent cytoplasmic factors - inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus - STAT, R-SMAD, NF-kB, Notch, TUBBY, NFAT

Roles and Conservation in Different Organisms

Transcription factors are essential for the regulation of gene expression and consequently are found in all living organisms. The Signal Transducers and Activator of Transcription (STAT also called signal transduction and transcription protein s regulate many aspects of Cell growth, survival and R-Smads or receptor regulated Smads are a class of proteins that include SMAD1, SMAD2, SMAD3, SMAD5, and SMAD9. NF-κB ( nuclear factor-kappa B) is a protein complex that is a Transcription factor. The tubby protein is an upstream Cell signaling Protein common to multicellular Eukaryotes The original tubby gene was identified in Nuclear factor of activated T-cells ( NFAT) is a general name applied to a family of Transcription factors shown to be important in Immune response. The number of transcription factors found within an organism increases with the genome size and the larger genomes tend to have more transcription factors per gene. ^[9]

There are approximately 2600 proteins in the human genome that contain DNA-binding domains and most of these are presumed to function as transcription factors. The human genome is the Genome of Homo sapiens, which is stored on 23 chromosome pairs ^[10] Therefore approximately 10% of genes in the genome code for transcription factors which makes this family the single largest family of human proteins. Furthermore genes are often flanked by several binding sites for distinct transcription factors and efficient expression of each these genes requires the cooperative action of several different transcription factors (see for example hepatocyte nuclear factors). Hepatocyte nuclear factors (HNFs are a group of phylogenetically unrelated Transcription factors that regulate the Transcription of a diverse group of Genes Hence the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development. Developmental Biology is the official journal of the Society for Developmental Biology. ^[7]

Transcription factors and human disease

Due to their important roles in development, intercellular signaling, and cell cycle, some human diseases have been associated with mutations in transcription factors. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Below are a few of the more well-studied examples:

• Rett syndrome Mutations in the MECP2 transcription factor are associated with Rett syndrome, a neurodevelopmental disorder. MECP2 ( methyl CpG binding protein 2 (Rett syndrome) is a Gene that provides instructions for making its Protein product MECP2 also referred Rett syndrome (also called Rett disorder) is a neurodevelopmental disorder that is classified as a Pervasive developmental disorder by the DSM-IV.

• Diabetes A rare form of diabetes called MODY (Maturity onset diabetes of the young) can be caused by mutations in hepatocyte nuclear factors (HNFs) or insulin promoter factor-1 (IPF1). Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Maturity onset diabetes of the young ( MODY) refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene Hepatocyte nuclear factors (HNFs are a group of phylogenetically unrelated Transcription factors that regulate the Transcription of a diverse group of Genes Pdx1 ( Pancreatic and duodenal homeobox 1) also known as insulin promoter factor 1, is a Transcription factor necessary for pancreatic development

• Developmental verbal dyspraxia Mutations in the FOXP2 transcription factor are associated with developmental verbal dyspraxia, a disease in which individuals are unable to produce the finely coordinated movements required for speech. FOXP2 (" forkhead box P2" is a Gene that is implicated in the development of language skills, including grammatical competence Developmental dyspraxia is one or all of a Heterogeneous range of Development disorders affecting the initiation organization and performance of action

• Autoimmune diseases Mutations in the FOXP3 transcription factor cause a rare form of autoimmune disease called IPEX. FOXP3 ( Forkhead box P3 is a Gene involved in Immune system responses Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body

• Cancer Many transcription factors are tumor suppressors or oncogenes, and thus mutations or aberrant regulation of them are associated with cancer. For example, Li-Fraumeni syndrome is caused by mutations in the tumor suppressor p53. Li-Fraumeni syndrome is a rare Autosomal dominant Hereditary disorder. p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene

Classification of transcription factors

Transcription factors are often classified based on the similarity of their DNA binding domains:^[11][12][13]

• 1 Superclass: Basic Domains (Basic-helix-loop-helix)
  • 1. A basic-helix-loop-helix (bHLH is a Protein Structural motif that characterizes a family of Transcription factors. 1 Class: Leucine zipper factors (bZIP)
    • 1. A leucine zipper, aka leucine scissors, is a super secondary Structural motif found in Proteins that creates adhesion forces in parallel The Basic Leucine Zipper Domain ( bZIP domain) is found in many DNA binding eukaryotic proteins 1. 1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
    • 1. In Molecular biology, c-Fos is a cellular Proto-oncogene belonging to the Immediate early gene family of Transcription factors c-Fos has a c-Jun is the name of a gene and protein which in combination with C-Fos, forms the AP-1 early response Transcription factor. 1. 2 Family: CREB
    • 1. CREB ( cAMP response element-binding Proteins are Transcription factors which bind to certain DNA sequences called CAMP response 1. 3 Family: C/EBP-like factors
    • 1. CCAAT-enhancer-binding proteins (or C/EBPs are a family of Transcription factors that are composed of six members C/EBP α to C/EBP ζ 1. 4 Family: bZIP / PAR
    • 1. PAR is a Transcription factor of the 1 Superclass of Basic Domains ( Basic-helix-loop-helix) 1. 5 Family: Plant G-box binding factors
    • 1. 1. 6 Family: ZIP only
  • 1. 2 Class: Helix-loop-helix factors (bHLH)
    • 1. A basic-helix-loop-helix (bHLH is a Protein Structural motif that characterizes a family of Transcription factors. 2. 1 Family: Ubiquitous (class A) factors
    • 1. 2. 2 Family: Myogenic transcription factors (MyoD)
    • 1. MyoD is a Protein with a key role in regulating Muscle 2. 3 Family: Achaete-Scute
    • 1. 2. 4 Family: Tal/Twist/Atonal/Hen
  • 1. 3 Class: Helix-loop-helix / leucine zipper factors (bHLH-ZIP)
    • 1. Basic helix-loop-helix leucine zipper transcription factors are as their name indicates Transcription factors containing both Basic helix-loop-helix and Leucine 3. 1 Family: Ubiquitous bHLH-ZIP factors; includes USF (USF1, USF2); SREBP (SREBP)
    • 1. Sterol Regulatory Element Binding Protein s ( SREBP s are Transcription factors that bind to the Sterol regulatory element DNA sequence 3. 2 Family: Cell-cycle controlling factors; includes c-Myc
  • 1. Myc (cMyc is a gene that regulates other genes It codes for a protein that binds to the DNA of other genes 4 Class: NF-1
    • 1. 4. 1 Family: NF-1 (NFIC)
  • 1. 5 Class: RF-X
    • 1. 5. 1 Family: RF-X (NFX2, NFX3, NFX5)
  • 1. 6 Class: bHSH

• 2 Superclass: Zinc-coordinating DNA-binding domains
  • 2. 1 Class: Cys4 zinc finger of nuclear receptor type
    • 2. A zinc finger is a large superfamily of Protein domains that can bind to DNA. In the field of Molecular biology, nuclear receptors are a class of Proteins found within the interior of cells that are responsible for sensing the presence of 1. 1 Family: Steroid hormone receptors
    • 2. Steroid hormone receptors are Intracellular receptors (typically Cytoplasmic that perform Signal transduction for Steroid hormones Steroid 1. 2 Family: Thyroid hormone receptor-like factors
  • 2. The thyroid hormone receptor is a type of Nuclear receptor that is activated by binding Thyroid hormone. 2 Class: diverse Cys4 zinc fingers
    • 2. 2. 1 Family: GATA-Factors
  • 2. GATA transcription factor s are a family of Transcription factors characterized by their ability to bind to the sequence "GATA" 3 Class: Cys2His2 zinc finger domain
    • 2. 3. 1 Family: Ubiquitous factors, includes TFIIIA, Sp1
    • 2. General transcription factor IIIA, also known as GTF3A, is a human Gene. See also SP1. Sp1 is a human Transcription factor involved in gene expression in the early development of an organism 3. 2 Family: Developmental / cell cycle regulators; includes Krüppel
    • 2. Krüppel is a Gap gene which encodes a Zinc finger protein with four tandemly repeated zinc finger domains 3. 4 Family: Large factors with NF-6B-like binding properties
  • 2. 4 Class: Cys6 cysteine-zinc cluster
  • 2. 5 Class: Zinc fingers of alternating composition

• 3 Superclass: Helix-turn-helix
  • 3. In Proteins the helix-turn-helix ( HTH) is a major Structural motif capable of binding DNA. 1 Class: Homeo domain
    • 3. A homeobox is a DNA sequence found within Genes that are involved in the regulation of patterns of development ( Morphogenesis) in Animals 1. 1 Family: Homeo domain only; includes Ubx
    • 3. Ultrabithorax or Ubx is a member of the Homeobox gene family In Drosophila melanogaster it is expressed in the T3 and A1 segments and represses wing 1. 2 Family: POU domain factors; includes Oct
    • 3. POU (pronounced 'pow' is a family of Proteins that have well-conserved Homeodomains Function POU Proteins are Eukaryotic An octamer transcription factor is a Transcription factor which binds to the "ATTTGCAT" sequence 1. 3 Family: Homeo domain with LIM region
    • 3. 1. 4 Family: homeo domain plus zinc finger motifs
  • 3. 2 Class: Paired box
    • 3. 2. 1 Family: Paired plus homeo domain
    • 3. 2. 2 Family: Paired domain only
  • 3. 3 Class: Fork head / winged helix
    • 3. FOX (Forkhead box Proteins are a family of Transcription factors that play important roles in regulating the expression of Genes involved in cell Consisting of about 110 Amino acids, the domain in winged-helix transcription factors has four helices and a two-strand Beta-sheet. 3. 1 Family: Developmental regulators; includes forkhead
    • 3. FOX (Forkhead box Proteins are a family of Transcription factors that play important roles in regulating the expression of Genes involved in cell 3. 2 Family: Tissue-specific regulators
    • 3. 3. 3 Family: Cell-cycle controlling factors
    • 3. 3. 0 Family: Other regulators
  • 3. 4 Class: Heat Shock Factors
    • 3. Heat shock factor (HSF in Molecular biology, is the name given to Transcription factors that regulate the expression of the Heat shock proteins. 4. 1 Family: HSF
  • 3. 5 Class: Tryptophan clusters
    • 3. 5. 1 Family: Myb
    • 3. 5. 2 Family: Ets-type
    • 3. 5. 3 Family: Interferon regulatory factors
  • 3. Interferon regulatory factors are proteins which regulate Transcription of Interferons (see Regulation of gene expression) 6 Class: TEA domain
    • 3. 6. 1 Family: TEA (TEAD1, TEAD2, TEAD3, TEAD4)

• 4 Superclass: beta-Scaffold Factors with Minor Groove Contacts
  • 4. 1 Class: RHR (Rel homology region)
    • 4. 1. 1 Family: Rel/ankyrin; NF-kappaB
    • 4. The ankyrin repeat is a 33-residue motif in Proteins consisting of two alpha helices separated by loops, first discovered in signaling NF-κB ( nuclear factor-kappa B) is a protein complex that is a Transcription factor. 1. 2 Family: ankyrin only
    • 4. 1. 3 Family: NF-AT (NFATC1, NFATC2, NFATC3)
  • 4. 2 Class: STAT
    • 4. 2. 1 Family: STAT
  • 4. The Signal Transducers and Activator of Transcription (STAT also called signal transduction and transcription protein s regulate many aspects of Cell growth, survival and 3 Class: p53
    • 4. 3. 1 Family: p53
  • 4. p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene 4 Class: MADS box
    • 4. MADS box is a conserved Sequence motif found in a family of Transcription factors the MADS-box Protein family 4. 1 Family: Regulators of differentiation; includes (Mef2)
      • 4. In the field of Molecular biology, myocyte enhancer factor-2 ( Mef2) Proteins are a family of Transcription factors which through control of 4. 2 Family: Responders to external signals, SRF (serum response factor) (SRF)
  • 4. 5 Class: beta-Barrel alpha-helix transcription factors
  • 4. 6 Class: TATA binding proteins
    • 4. The TATA binding protein ( TBP) is a Transcription factor that binds specifically to a DNA sequence called the TATA box. 6. 1 Family: TBP
    • 4. 7. 1 Family: SOX genes, SRY
    • 4. SOX genes encode a family of Transcription factors that bind to the Minor groove in DNA, and belong to a super-family of Genes characterized SRY ( Sex-determining Region Y) is a Sex -determining Gene on the Y chromosome in the Therians (placental mammals and marsupials 7. 2 Family: TCF-1 (TCF1)
    • 4. 7. 3 Family: HMG2-related, SSRP1 (SSRP1)
    • 4. 7. 5 Family: MATA
  • 4. 8 Class: Heteromeric CCAAT factors
    • 4. 8. 1 Family: Heteromeric CCAAT factors
  • 4. 9 Class: Grainyhead
    • 4. 9. 1 Family: Grainyhead
  • 4. 10 Class: Cold-shock domain factors
    • 4. 10. 1 Family: csd
  • 4. 11 Class: Runt
    • 4. 11. 1 Family: Runt

• 0 Superclass: Other Transcription Factors
  • 0. 1 Class: Copper fist proteins
  • 0. 2 Class: HMGI(Y) (HMGA1)
    • 0. 2. 1 Family: HMGI(Y)
  • 0. 3 Class: Pocket domain
  • 0. 4 Class: E1A-like factors
  • 0. 5 Class: AP2/EREBP-related factors
    • 0. 5. 1 Family: AP2
    • 0. 5. 2 Family: EREBP
    • 0. 5. 3 Superfamily: AP2/B3
      • 0. The B3 DNA binding domain (DBD is a highly conserved domain exclusively found in Transcription factors from Higher plants (≥40 species 5. 3. 1 Family: ARF
      • 0. 5. 3. 2 Family: ABI
      • 0. 5. 3. 3 Family: RAV

See also

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References

External links

• MeSH Transcription+Factors
• DBD: Transcription factor database Home. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Retrieved on 2008-03-02. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 986 - Louis V becomes King of the Franks. 1127 - Assassination of Charles the Good ^[1]
• Gilbert FS. Transcription factors: DevBio on-line supplementary material to Developmental Biology. Sinauer Associates. Retrieved on 2008-03-02. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 986 - Louis V becomes King of the Franks. 1127 - Assassination of Charles the Good ^[2]
• Transcription Factor Classification, A classification of transcription factors based on their DNA-binding domains. BIOBASE GmbH (2002-10-01). See also 2002 (disambiguation Year 2002 ( MMII) was a Common year starting on Tuesday of the Gregorian calendar. Events 331 BC - Alexander the Great defeats Darius III of Persia in the Battle of Gaugamela. Retrieved on 2008-03-02. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 986 - Louis V becomes King of the Franks. 1127 - Assassination of Charles the Good ^[3]
• Image of transcription factor function in humans. Access Excellence, The Nation Health Museum. Retrieved on 2008-03-02. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 986 - Louis V becomes King of the Franks. 1127 - Assassination of Charles the Good Figure 8-10 from Essential cell biology. ^[4]