What are the two main types of transcription factors?
Transcription factors are modular in nature in all organisms. In general, they have a DNA binding domain, one or more transcription activation and/or repressor domain, and often a dimerization domain. In many cases, transcription factors also have other protein-protein interaction domain(s).
Transcription factors are modular in nature in all organisms. In general, they have a DNA binding domain, one or more transcription activation and/or repressor domain, and often a dimerization domain. In many cases, transcription factors also have other protein-protein interaction domain(s).
Some transcription factors are general ones that are found in virtually all cells of an organism. Other transcription factors are specific for certain types of cells and stages of development.
According to recent data, the human genome encodes about 1500 regulatory sequence-specific DNA-binding factors (transcription factors, TFs) [7–9]. TFs constitute a large functional family of proteins directly regulating the activity of genes.
Transcription has three stages: initiation, elongation, and termination.
| Transcription Factor Family | Subtype | Role in Development |
|---|---|---|
| GATA | GATA2 | Hematopoiesis [111] |
| GATA3 | T-cell lymphopoiesis, self-renewal, and differentiation of long-term HSCs [115] | |
| GATA4 | Cardiac angiogenesis and bile hom*oeostasis [117,118] | |
| GATA5 | Cardiac development [121,122] |
TFClass is a classification of eukaryotic transcription factors based on the characteristics of their DNA-binding domains. It comprises four general levels (superclass, class, family, subfamily) and two levels of instantiation (genus and molecular species). Two of them (subfamily and factor species) are optional.
The holoenzyme consists of a preformed complex of RNA polymerase II, the general transcription factors TFIIB, TFIIE, TFIIF, and TFIIH, and several other proteins that activate transcription.
Transcription factors are proteins that help turn specific genes "on" or "off" by binding to nearby DNA. Transcription factors that are activators boost a gene's transcription. Repressors decrease transcription.
Gene regulatory programs in distinct cell types are maintained in large part through the cell-type–specific binding of transcription factors (TFs). The determinants of TF binding include direct DNA sequence preferences, DNA sequence preferences of cofactors, and the local cell-dependent chromatin context.
How do you identify transcription factors?
The ChIP assay is a very powerful technique used to identify regions of a genome associated with specific proteins including but not limited to transcription factors within their native chromatin context (1). In this technique, intact cells are fixed with formaldehyde to cross-link proteins with their associated DNA.
The four transcription factors OCT4, SOX2, KLF4, and MYC (OSKM) together can convert human fibroblasts to induced pluripotent stem cells (iPSCs).
Some transcription factors are general ones that are found in virtually all cells of an organism. Other transcription factors are specific for certain types of cells and stages of development.
RNA polymerases I and III transcribe the genes encoding transfer RNA, ribosomal RNA, and various small RNAs. RNA polymerase II transcribes the vast majority of genes, including all those that encode proteins, and our subsequent discussion therefore focuses on this enzyme.
Transcription occurs in the three steps—initiation, elongation, and termination—all shown here. Transcription takes place in three steps: initiation, elongation, and termination. The steps are illustrated in Figure 2.
Transcription is carried out by an enzyme called RNA polymerase and a number of accessory proteins called transcription factors.
Transcription factors (TFs) recognize specific DNA sequences to control chromatin and transcription, forming a complex system that guides expression of the genome.
Arguably p53's most important function is to act as a transcription factor that directly regulates perhaps several hundred of the cell's RNA polymerase II (RNAP II)-transcribed genes, and indirectly regulates thousands of others. Indeed p53 is the most well studied mammalian transcription factor.
The sine oculis (SIX) family of transcription factors are key regulators of developmental processes during embryogenesis. Members of this family control gene expression to promote self-renewal of progenitor cell populations and govern mechanisms of cell differentiation.
The general transcription factors comprise at least six distinct species: TFII A, B, D, E, F, and H (see Fig. 7.1b). TFIID (300–750 kDa) is a multiprotein complex composed of a TATA (box)-binding protein (TBP) and up to 13 TBP-associated factors (TAFs).
How are transcription factors regulated?
The activity of a transcription factor is often regulated by (de) phosphorylation, which may affect different functions, e.g. nuclear localization DNA binding and trans-activation. Ligand binding is another mode of transcription-factor activation. It is typical for the large super-family of nuclear hormone receptors.
Nuclear receptors are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various other lipid-soluble signals, including retinoic acid, oxysterols, and thyroid hormone (Mangelsdorf et al. 1995).
Several protein transcription factors may bind to the same gene promoter region that corresponds to network interactions “TFs–gene”. One TF may have several gene targets that corresponds to “TF–genes” interactions. Protein TF may bind to the promoter of its own gene, thus forming a regulatory contour in gene network.
Genetic variation may contribute to disease largely through misregulation of gene expression. Mutations in the transcription factors that control cell state may impact the autoregulatory loops that are at the core of cellular regulatory circuitry, leading to the loss of a normal healthy cell state.
Mutated or dysregulated transcription factors represent a unique class of drug targets that mediate aberrant gene expression, including blockade of differentiation and cell death gene expression programmes, hallmark properties of cancers.
