Figure 1. Transcription factors activate DNA transcription. (From Wikimedia Commons)
Transcription factors are the direct interpretation of the genome and the first step in the execution of DNA decoding sequences. Many transcription factors act as major regulators and select genes, controlling the determination of cell types, developmental patterns, and processes that control specific pathways (such as immune response). In the laboratory, transcription factors can promote cell differentiation, dedifferentiation and transdifferentiation. Mutations in transcription factors and transcription factor binding sites are the main factors causing human disease. In metazoans, the physiological role of their protein sequence regulatory regions is usually very conservative, suggesting that the genome regulatory "network" may also be conservative. However, the conversion rate of individual regulatory sequences is very high, and multiple copies and mutations of transcription factors may occur when the time scale is longer. The same transcription factor can regulate different genes in different cell types (for example, ESR1 in breast and endometrial cell lines), indicating that the regulation of transcription factors is dynamic even in the same organism. Determining how transcription factors are assembled in different ways to identify binding sites and regulate "network" transcription is a huge and daunting task, but it is essential to understand their physiological functions and to decode the specific functions of the genome. and the choreography of highly specific expression programs in complex organisms. Compared with other sequences, transcription factors have a 1000-fold or even higher preference for specific binding sequences, because transcription factors can play a role by blocking DNA binding sites of other proteins, and the ability to bind specific DNA sequences alone is often regarded as an indicator of transcriptional ability. Without detailed information about the DNA sequence bound by transcription factors, these proteins cannot be understood functionally. The binding of transcription factors to specific DNA is usually summed up as "motif", refers to a model of a group of related short sequences given TF priority, which can be used to scan longer sequences to identify potential binding sites. The identification of DNA-bound motif is usually the first step in explaining the function of transcription factors in detail, and the identification of potential binding sites provides a way for further analysis. Transcription factors can be classified according to the mechanical, functional, and even structural properties of their DNA-binding domains. The mechanical properties are related to the physical position of the transcription factor binding site on the DNA sequence, and the functional properties are related to the role of transcription factors in transcriptional regulation. Therefore, if we know the category of transcription factors, we can better understand the mechanism of transcriptional regulation.
Transcription factor binding site
The transcription factor binding site is the DNA region that binds to the gene template chain when the transcription factor regulates gene expression. According to the previous conclusion, the binding sites of transcription factors should generally be located at the 5 'end of the gene. However, the latest study found that only 22% of the transcription factor binding sites on human chromosomes 21 and 22 are located at the 5 'end of the protein coding gene. A transcription factor can often regulate the expression of several genes at the same time, and its binding sites on different genes are conservative, but they are not exactly the same.
Figure 2. Schematic of a prototypical TF. (Lambert S A, et al. 2018)
Classification of transcription factors based on DNA binding domain
The general classification of transcription factors is based on the similarity of their DNA-binding domains. PhilipStegmaier et al constructed a hidden Markov model and used it to classify transcription factors. They divided the transcription factors of several species into four categories:
Figure 3. Collection of 7 putative DM human TFs out of 7 considered proteins. (From humantfs.)
Classification of transcription factors based on the necessity of transcriptional initiation
When eukaryotes transcribe. The synergistic effect of multiple transcription factors is often needed. Whether a protein is part of a transcriptional regulatory mechanism is often seen through the in vitro system to see whether it is necessary for the transcriptional initiation process. These transcription factors that play an important role in the process of transcription can be divided into two categories:
(1) Subunits of RNA polymerase. The subunit of RNA polymerase is necessary in the process of transcription, but it is not specific to a certain promoter, but recognizes the promoter in the process of transcription and enhances the interaction between RNA polymerase and promoter.
(2) Binding to RNA polymerase to form the initial complex. Some transcription factors can bind to RNA polymerase to form initial complex, but do not form the components of free polymerase. These transcription factors may be necessary for all promoters to initiate transcription, but they may only be necessary for example, transcriptional termination. However, in this kind of transcription factors, it is difficult to strictly distinguish which subunits are RNA polymerase subunits and which are only cofactors.
(3) It only binds to the specific sequence in the promoter of its sacrificial gene. Some transcription factors bind only to specific sequences in their gene promoters. If these sequences are stored. If it lies in the promoter, the transcription factor is part of the general transcriptional regulatory mechanism. If these sequences exist only in some kinds of promoters, it is necessary to identify the transcription factors of this search sequence only for the initial transcription of these specific promoters.
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