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In the field of Molecular Biology , a transcription factor is a Protein that binds to specific parts of DNA using DNA Binding Domain s and is part of the system that controls the transfer (or Transcription ) of genetic information from DNA to RNA .12 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 , a protein which Transcribes genetic information.34 DNA BINDING DOMAINS The portion ( Domain ) of the transcription factor that binds DNA is called its DNA binding domain. Below is a partial list of some of the major families of DNA-binding domains/transcription factors:
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 Domain s.5 (for example Coactivator s, Chromatin Remodeler s, Histone Acetylases , Deacetylases , Kinase s, and Methylase s). 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 . 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 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. It is unlikely, however, that a transcription factor binds all compatible sequences in the Genome of the Cell . Other constraints, such as DNA accessibility in the cell or availability of Cofactor s 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. STRUCTURE Transcription factors are modular in structure and contain the following Domains :
MECHANISM OF ACTION Transcription factors may be activated (or deactivated) through their signal sensing domain by a number of mechanisms including:
The resulting activated transcription factors through their DBD bind to specific sequences of DNA upstream or downstream to the gene they regulate and then either enhance or repress transcription of these genes by assisting or blocking RNA polymerase binding respectively. A cluster of transcription factors is the Preinitiation Complex (PIC) that recruits and activates RNA Polymerase . Conversely, repressor transcription factors inhibit transcription by blocking the attachment of activator proteins. The regulation of transcription is a highly complex process as it is dependent upon a number of factors including which transcription factors and other coregulatory proteins are present within a particular cell as well as the local 3-dimensional structure of the gene ( Chromatin ). Initial models, based on ''in vitro'' experiments suggested that the assembly of transcription factors dictated by the DNA sequence. It is, however, becoming increasingly obvious that the events leading to activation of transcription are dependent on a large number of factors and are highly intertwined. Furthermore Epigenetic information present on DNA appears to play an important role in transcriptional activation. CLASSES Mechanistic There are three mechanistic classes of transcription factors:8
Functional Alternatively transcription factors have been classified according to their regulatory function:
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 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.10 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.11 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 ). 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 . CLASSIFICATION OF TRANSCRIPTION FACTORS Transcription factors are often classified based on the similarity of their DNA binding domains:1213
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