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Transcription factors

Transcription factors (transcription factors) are proteins that control the synthesis of mRNA on a DNA template ( transcription ) by binding to specific DNA segments [1] [2] . Transcription factors perform their function either alone or in combination with other proteins. They provide a reduction ( repressors ) or increase ( activators ) of the binding constant of RNA polymerase with the regulatory sequences of the regulated gene [3] [4] [5] .

The defining feature of transcription factors is the presence in their composition of one or more DNA-binding domains that interact with characteristic DNA regions located in the regulatory regions of the genes. Other proteins that play a key role in the regulation of gene expression , such as coactivators , histone acetylases , kinases , methylases , do not have DNA-binding domains, and therefore cannot be counted as transcription factors [6] [7] [8] .

The structure of the complex TATA-binding protein / transcription factor TF (II) B from the archaea Pyrococcus woesei with DNA according to the results of x-ray analysis . Top - a schematic depiction of the tertiary structure , below - the molecular surface of the complex

Conservatism in various organisms

Transcription factors are necessary for the regulation of gene expression and are found in all living organisms. Their number, both absolute and specific, increases with increasing genome size [9] .

More than 2,600 proteins with a DNA-binding domain have been found in the human genome , and most of them are thought to be transcription factors [10] . Consequently, about 10% of all genes in the genome encode transcription factors. Thus, they are the largest family of human proteins [11] . Moreover, the activity of many genes is regulated by the corporate interaction of a large number of different transcription factors, which allows each of the genes to provide a unique method of regulation in the process of development of the organism [8] .

Functions

Transcription factors are one of the groups of proteins that provide the reading and interpretation of genetic information. They bind DNA and help initiate a program to increase or decrease gene transcription. Thus, they are vital for the normal functioning of the body at all levels. The following are the most important processes in which transcription factors are involved.

Regulation of basal gene expression

Background transcriptional activity is provided by a set of TF common to all genes. An important class of eukaryotic transcription factors is GTFs (general transcription factors) [12] [13] . Many of its representatives do not bind DNA directly, but are part of the transcription initiation complex (pre-initiation complex), which directly interacts with RNA polymerase. The most common GTFs are TFIIA , TFIIB , TFIID (associated with the so-called TATA box ( promoter element)), TFIIE , TFIIF , and TFIIH [14] .

In addition to the TF required for the expression of all genes, there are also specific transcription factors that enable / disable specific genes at the right time.

Regulation of ontogenesis

Many TFs of multicellular organisms are involved in ensuring their development [15] . Acting in accordance with the genetic program and / or in response to external influences, they initiate or suppress the transcription of certain genes, which entails changes in cell morphology, cell differentiation, morphogenesis , organogenesis , etc. For example, a family of homeobox TFs is critical for the formation of a correct body morphology in organisms from Drosophila to humans [16] [17] . Mutations of the genes of these proteins ( homeotic mutations ) in Drosophila lead to serious disturbances in the differentiation of body segments of these insects (for example, the development of legs instead of antennae).

Another example of this group of TFs is the gene product of the determining region Y (SRY, Sex-Determining Region Y), which plays an important role in determining the sex of a person. [18]

Response to extracellular signals

The coordinated regulation of the interaction of cells of a multicellular organism is carried out by the release of special molecules ( hormones , cytokines , etc.), which cause a signaling cascade in target cells. In the event that a signal causes a change in the expression level of certain genes, the end stage of the cascade is often TF [19] . The estrogen signaling pathway is an example of a short cascade that includes the estrogen receptor transcription factor: estrogen is secreted by the tissues of the placenta and the ovary, overcomes the plasma membrane of the recipient cells, and binds to its receptor in the cytoplasm. The estrogen receptor penetrates into the nucleus and binds a specific region of DNA, changing the transcriptional regulation of the corresponding gene [20] .

Responding to environmental change

TFs are not the only end links of signaling cascades arising in response to various external stimuli, but they can also be effectors in signaling cascades induced by environmental exposure. For example, heat shock factor (HSF) activates heat shock protein genes that ensure survival when temperature rises (for example, chaperones ) [21] , hypoxia-induced factor (HIF) —when oxygen concentration decreases [22] ; Protein SREBP (sterol regulatory element binding protein) helps to maintain the required lipid content in cells [23] .

Cell cycle control

Many TFs, especially oncogenes and oncosuppressors, are involved in the regulation of the cell cycle . They determine the transition from one phase of the cell cycle to another, the frequency of divisions and the intensity of growth. One of the most well-known such TFs is the Myc oncogene, which plays an important role in the growth of cells and their direction into apoptosis .

Regulation

All general biological processes have multi-level regulation and control. This is also true for TF - TF not only regulates the level of accumulation of proteins and RNA in the cell, but also regulates the activity of its own genes (often with the help of other TFs). The following briefly describes the main ways of regulating the activity of TF.

Common to all proteins

The level of accumulation of TF in the cell is regulated according to the same pattern as that of other proteins due to the control of transcription, mRNA degradation, translation , post-processing of the protein, its intracellular localization and degradation. Self-regulation is possible according to the negative feedback principle - TF represses the activity of the gene encoding it.

Intranuclear Localization

In eukaryotic organisms, the processes of transcription and translation are spatially separated - they occur in the nucleus and cytoplasm, respectively. After synthesis, TFs should penetrate into the nucleus, breaking the double membrane. Many proteins that function in the nucleus have a nuclear localization signal — a specific portion of the polypeptide chain that targets the protein to the nucleus. For many TF translocation is a key factor in the regulation of their activity [24] . Important classes of TF, such as some nuclear receptors, must first bind the endogenous agonist ligand in the cytoplasm and only then be transported to the nucleus [24] .

Activation

TFs can be activated / deactivated by affecting their signal-sensitive domain in various ways:

  • ligand binding - essential for the functioning of the substance, not part of the polypeptide (for example, Zn 2+ ions )
  • phosphorylation [25] [26] - many TF must be phosphorylated to be able to bind DNA.
  • interaction with other TF and / or coregulatory proteins.

Accessibility of the DNA binding site

In eukaryotes, genes that are not permanently transcribed are often found in heterochromatin (DNA regions tightly packed by histone binding and organized into compact chromatin fibrils). Heterochromatin DNA is not available for many transcription factors. In order for TFs to bind to DNA, heterochromatin must be transformed into euchromatin , usually by histone modifications. Also, for the binding of TF with DNA, chromatin freedom from nucleosomes plays an important role. Chromatin free from nucleosomes is called open chromatin and much more often binds transcription factors than is associated with chromatin nucleosomes. Nucleosome redistribution is performed by chromatin remodeling factors. A TF binding site on DNA may be unavailable even if it is linked by another transcription factor. Pairs of transcription factors may play an antagonistic role (activator - repressor) in the regulation of single gene activity.

Presence of other cofactors / transcription factors

Most tf do not work alone. Often, to activate transcription of a gene, a large amount of TF must be associated with its regulatory elements. The binding of TF causes the involvement of intermediate proteins, such as cofactors, which leads to the assembly of the pre-initiation complex and the landing on the RNA polymerase promoter.

Structure

TFs are modular in structure and contain the following domains [1] :

  • DNA-binding domain (DBD) - interacts with specific DNA sequences characteristic of promoters and enhancers . The specificity of recognition of certain sequences determines the set of genes that are subject to regulation by this TF;
  • transactivating domain (TAD) - contains binding sites for other proteins, for example, transcriptional coregulators [27] ;
  • a signal-recognition domain (SSD) (for example, a ligand-binding domain) that is sensitive to external signals and is responsible for transmitting the signal to other components of the transcriptional complex, which causes an increase or decrease in the expression level.

DNA binding domain

The structural-functional unit (domain) of transcription factors that binds DNA is called the DNA-binding domain. Below is a list of the most important families of DNA-binding domains / TF:

FamilyNCBI conserved domainsProtein Structural Classification Database (SCOP)InterPro Database
Helix-loop-helix [28]cl0022847460IPR001092
Leucine Zipper [29]cl0257657959IPR004827
C-terminal effector domains of compound response regulators46894IPR001789
GCC boxcl0003354175
Spiral twist-spiral (helix-turn-helix) [30]cl02600
Homeodomain proteins - bind the homeobox (a special piece of DNA). They play a critical role in the individual development of organisms ( ontogenesis ). [31]cd0008646689IPR009057
Similar to the phage lambda repressor47413IPR010982
srf-likecl0010955455IPR002100
Doubles [32]cl09102
winged helix46785IPR011991
Zinc Fingers [33]
* multi-domain zinc fingers type Cys 2 His 2 [34]pfam0009657667IPR007087
* Zn 2 / Cys 657701
* Zinc fingers type Zn 2 / Cys 8 nuclear hormone receptorspfam0010557716IPR001628

TF binding sites

DNA segments that interact with transcription factors are called TF binding sites. The interaction is carried out by electrostatic forces , hydrogen bonds and van der Waals forces . Due to the corporate, sterically determined action of these forces, which is determined by the spatial structure of the protein molecule, TF can bind only certain sections of DNA. Not all nucleotide bases in DNA entering the TF binding site have the same significance when interacting with protein. As a result, TF usually associate not a plot with a strictly defined primary structure, but a group of structures with close similarity, each with a different degree of affinity. For example, although the consensus sequence for the binding site of TATA-binding proteins is TATAAAA, they can also interact with TATATAT and TATATAA.

Due to the fact that TF interact with short portions of the DNA of a heterogeneous structure, potential TF binding sites can occur randomly in a sufficiently long DNA molecule. It is unlikely, however, that TF interact with all relevant elements in the genome.

Various restrictions, such as the availability of sites and the presence of cofactors, can contribute to the direction of TF in the right parts of DNA. Thus, it is difficult, based on the genome sequence, to reliably predict the actual site of TF landing on DNA in vivo . Additional TF specificity may be mediated by the presence of several DNA binding domains within a single protein that interact with two or more contiguous sequences simultaneously.

Clinical aspects

In connection with the key role of TF in the process of implementing hereditary information, some human diseases can be caused by mutations in TF genes. Below are some of the most studied violations of this kind:

  • Rett syndrome . Mutations in the TF gene MECP2 are associated with Rett syndrome, a disorder in the development of the nervous system [35] .
  • Diabetes A rare form of diabetes called MODY (Maturity onset diabetes of the young) may be due to mutations in the genes of some TFs [36] .
  • Developmental verbal dyspraxia . (violation of speech functions). Mutations in the TF FOXP2 gene are associated with the development of this disease, in which a person cannot produce the coordinated movements necessary for speech function [37] [38] .
  • Autoimmune diseases . Mutations in the TF FOXP3 gene are associated with IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked syndrome) autoimmune disease [38] .
  • Cancer Many transcription factors are oncogenes or tumor suppressors, and their mutations or improper regulation can lead to the development of cancer. For example, Li-Fraumeni syndrome is caused by mutations in the p53 tumor suppressor gene [39] .

Classification

TFs can be classified by (1) the mechanism of action, (2) the regulatory function, (3) the structure of the DNA-binding domain, as well as natural and (5) artificial.

Mechanism of Action

On this basis, there are three classes of TF:

  • The main transcription factors (GTFs) involved in the formation of the initiation complex. The most important of these are TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. They are present in all cells and interact with the promoter core of genes transcribed by second-class RNA polymerase.
  • TF interacting with upstream DNA regions (regions up to the promoter, lying relative to it on the other side of the coding region of the gene ).
  • Induced TF are similar to the previous class, but require activation or inhibition.

Function

  1. Constitutive - always present in all cells - the main factors of transcription, Sp1 , NF1 , CCAAT .
  2. Activated (active in certain conditions)
    1. Participating in the development of the organism (cell-specific) - expression is strictly controlled, but, starting to express, do not require additional activation - GATA, HNF, PIT-1, MyoD, Myf5, Hox, Winged Helix.
    2. Signal Dependent - require an external signal to activate
      1. extracellular signal-dependent - nuclear receptors
      2. intracellular signal-dependent - activated by low molecular weight intracellular compounds - SREBP , p53 , single nuclear receptors
      3. membrane-bound receptor-dependent - phosphorylated by kinases of the signaling cascade
        1. resident nuclear factors - are in the core, regardless of activation - CREB, AP-1, Mef2
        2. latent cytoplasmic factors - in an inactive state are localized in the cytoplasm, after activation are transported into the nucleus - STAT, R-SMAD, NF-kB , Notch , TUBBY, NFAT.

Structural Classification

 
DNA-binding domain of the " leucine zipper " type in complex with DNA. Above - a schematic depiction of the molecular surface, below - the tertiary structure of the complex.
 
DNA-binding domain of the " helix-loop-helix " in complex with DNA. At the top - a schematic depiction of the tertiary structure, at the bottom - the molecular surface of the complex.

Transcription factors are classified based on the similarity of the primary structure (which also implies the similarity of the tertiary structure) of DNA-binding domains [40] [41] [42] .

  • 1 Superclass: Basic Domains ( Basic-helix-loop-helix )
    • 1.1 Class: Leucine Zipper ( bZIP )
      • 1.1.1 Family: AP-1 (-like) components; includes ( c-Fos / c-Jun )
      • 1.1.2 Family: CREB
      • 1.1.3 Family: C / EBP- like factors
      • 1.1.4 Family: bZIP / PAR
      • 1.1.5 Family: Plant G-box binding factors
      • 1.1.6 Family: ZIP only
    • 1.2 Class: Spiral-loop-spiral ( bHLH )
      • 1.2.1 Family: Ubiquitous (Class A) factors
      • 1.2.2 Family: Myogenic transcription factors ( MyoD )
      • 1.2.3 Family: Achaete-Scute
      • 1.2.4 Family: Tal / Twist / Atonal / Hen
    • 1.3 Class: Spiral-loop-Spiral / Leucine Zipper Factors ( bHLH-ZIP )
      • 1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF ( USF1 , USF2 ); SREBP ( SREBP )
      • 1.3.2 Family: Cell-cycle controlling factors; includes c-Myc
    • 1.4 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
      • 2.1.1 Family: Steroid hormone receptors
      • 2.1.2 Family: Thyroid hormone receptor- like factors
    • 2.2 Class: diverse Cys4 zinc fingers
      • 2.2.1 Family: GATA-Factors
    • 2.3 Class: Cys2His2 zinc finger domain
      • 2.3.1 Family: Ubiquitous factors, includes TFIIIA , Sp1
      • 2.3.2 Family: Developmental / cell cycle regulators; includes Krüppel
      • 2.3.4 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: Spiral-twist-spiral
    • 3.1 Class: Homeodomain
      • 3.1.1 Family: Homeo domain only; includes Ubx
      • 3.1.2 Family: POU domain factors; includes Oct
      • 3.1.3 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
      • 3.3.1 Family: Developmental regulators; includes forkhead
      • 3.3.2 Family: Tissue-specific regulators
      • 3.3.3 Family: Cell-cycle controlling factors
      • 3.3.0 Family: Other regulators
    • 3.4 Class: Heat Shock Factors
      • 3.4.1 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
    • 3.6 Class: TEA (transcriptional enhancer factor) 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
      • 4.1.2 Family: ankyrin only
      • 4.1.3 Family: NF-AT ( N uclear F actor of A c T -cells) ( NFATC1 , NFATC2 , NFATC3 )
    • 4.2 Class: STAT
      • 4.2.1 Family: STAT
    • 4.3 Class: p53
      • 4.3.1 Family: p53
    • 4.4 Class: MADS box
      • 4.4.1 Family: Regulators of differentiation; includes ( Mef2 )
        • 4.4.2 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
      • 4.6.1 Family: TBP
      • 4.7.1 Family: SOX genes , SRY
      • 4.7.2 Family: TCF-1 ( TCF1 )
      • 4.7.3 Family: HMG2-related, 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
        • 0.5.3.1 Family: ARF
        • 0.5.3.2 Family: ABI
        • 0.5.3.3 Family: RAV

Artificial transcription factors

The CRISPR system can be adapted to act as a transcription factor (crisprTF). For this, the CRISPR-associated protein, known as Cas9 , is altered so that it can no longer cleave it after binding to DNA. Then a segment is added to it that activates or suppresses gene expression by modulating the cell's transcriptional mechanism [43] [44] [45] [46] . Unlike transcription factors based on zinc fingers and the , for the recognition of DNA by the CRISPR-Cas system, only the creation of an appropriate RNA “guide” sequence is required, rather than the creation of new protein domains of the enzyme, which makes it much more accessible cheapness and simplicity (up to the fact that a set of rules is developed - “grammar” - describing how to design a synthetic transcription factor (STFS) and a program for its computer-aided design [47] ).

See also

  • NPAS3
  • Polycomb group proteins
  • Regulatory function of proteins
  • Lactose Operon
  • Oct-4

Notes

  1. ↑ 1 2 Latchman DS Transcription factors: an overview (Eng.) // Int. J. Biochem. Cell Biol. : journal. - 1997. - Vol. 29 , no. 12 - P. 1305-1312 . - DOI : 10.1016 / S1357-2725 (97) 00085-X . - PMID 9570129 .
  2. ↑ Karin M. Too many transcription factors: positive and negative interactions (Eng.) // New Biol. : journal. - 1990. - Vol. 2 , no. 2 - P. 126-131 . - PMID 2128034 .
  3. ↑ Roeder RG The role of general initiation factors in transcription by RNA polymerase II (Eng.) // Trends Biochem. Sci. : journal. - 1996. - Vol. 21 , no. 9 - P. 327—335 . - DOI : 10.1016 / 0968-0004 (96) 10050-5 . - PMID 8870495 .
  4. ↑ Nikolov DB, Burley SK RNA polymerase II transcription initiation: a structural view (Eng.) // Proceedings of the United States of America : journal. - 1997. - Vol. 94 , no. 1 . - P. 15-22 . - DOI : 10.1073 / pnas.94.1.15 . - PMID 8990153 .
  5. ↑ Lee TI, Young RA Transcription of eukaryotic protein-coding genes (English) // Annu. Rev. Genet. : journal. - 2000. - Vol. 34 - p . 77-137 . - DOI : 10.1146 / annurev.genet.34.1.77 . - PMID 11092823 .
  6. ↑ Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins (Eng.) // Science: journal. - 1989. - Vol. 245 , no. 4916 . - P. 371-378 . - DOI : 10.1126 / science.2667136 . - PMID 2667136 .
  7. Ptashne M., Gann A. Transcriptional activation by recruitment (English) // Nature. - 1997. - Vol. 386 , no. 6625 . P. 569-577 - DOI : 10.1038 / 386569a0 . - PMID 9121580 .
  8. ↑ 1 2 Brivanlou AH, Darnell JE Signal transduction and science control // Science: journal. - 2002. - Vol. 295 , no. 5556 . - P. 813-818 . - DOI : 10.1126 / science.1066355 . - PMID 11823631 .
  9. ↑ van Nimwegen E. Scaling laws in the functional content of genomes (English) // Trends Genet. : journal. - 2003. - Vol. 19 , no. 9 - P. 479-484 . - DOI : 10.1016 / S0168-9525 (03) 00203-8 . - PMID 12957540 .
  10. ↑ Babu MM, Luscombe NM, Aravind L., Gerstein M., Teichmann SA Structure and evolution of transcriptional regulatory networks (Eng.) // Curr. Opin. Struct. Biol. : journal. - 2004. - Vol. 14 , no. 3 - P. 283-291 . - DOI : 10.1016 / j.sbi 2004.05.004 . - PMID 15193307 .
  11. ↑ Lambert SA , Jolma A. , Campitelli LF , Das PK , Yin Y. , Albu M. , Chen X. , Taipale J. , Hughes TR , Weirauch MT The Human Transcription Factors. (English) // Cell. - 2018. - 8 February ( vol. 172 , no. 4 ). - P. 650-665 . - DOI : 10.1016 / j.cell.2018.01.029 . - PMID 29425488 .
  12. ↑ Reese JC Basal transcription factors (Neopr.) // Current opinion in genetics & development. - 2003. - April ( vol. 13 , No. 2 ). - p . 114-118 . - DOI : 10.1016 / S0959-437X (03) 00013-3 . - PMID 12672487 .
  13. Ila Shilatifard A., Conaway RC, Conaway JW The RNA polymerase II elongation complex (English) // Annual review of biochemistry : journal. - 2003. - Vol. 72 . - p . 693-715 . - DOI : 10.1146 / annurev.biochem.72.12180101.161551 . - PMID 12676794 .
  14. MC Thomas MC, Chiang CM The general transcription machinery and general cofactors (Eng.) // Critical reviews in biochemistry and molecular biology: journal. - 2006. - Vol. 41 , no. 3 - P. 105—178 . - PMID 16858867 .
  15. ↑ Lobe CG Transcription factors and mammalian development (Neopr.) // Current topics in developmental biology. - 1992. - T. 27 . - p . 351-338 . - PMID 1424766 .
  16. ↑ Lemons D., McGinnis W. Genomic evolution of Hox gene clusters (eng.) // Science : journal. - 2006. - September ( vol. 313 , no. 5795 ). - P. 1918-1922 . - DOI : 10.1126 / science.1132040 . - PMID 17008523 .
  17. ↑ Moens CB, Selleri L. Hox cofactors in vertebrate development (Unidentified) // Developmental biology. - 2006. - March ( t. 291 , № 2 ). - p . 193-206 . - DOI : 10.1016 / j.ydbio.2005.10.032 . - PMID 16515781 .
  18. ↑ Ottolenghi C., Uda M., Crisponi L., Omari S., Cao A., Forabosco A., Schlessinger D. Determination and stability of sex (Neopr.) // BioEssays: biology. - 2007. - January ( t. 29 , № 1 ). - pp . 15-25 . - DOI : 10.1002 / bies.20515 . - PMID 17187356 .
  19. ↑ Pawson T. Signal transduction - a conserved pathway from the membrane to the nucleus (English) // Developmental genetics: journal. - 1993. - Vol. 14 , no. 5 - P. 333—338 . - DOI : 10.1002 / dvg.1020140502 . - PMID 8293575 .
  20. ↑ Osborne CK, Schiff R., Fuqua SA, Shou J. Estrogen receptor: current understanding of activation and modulation (Eng.) // Clin. Cancer Res. : journal. - 2001. - December ( vol. 7 , no. 12 Suppl ). - P. 4338s — 4342s; discussion 4411s — 4412s . - PMID 11916222 .
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  23. ↑ Weber LW, M. Boll, Stamp A. Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins (English) // World J. Gastroenterol. : journal. - 2004. - November ( vol. 10 , no. 21 ). - P. 3081-3087 . - PMID 15457548 .
  24. 2 1 2 Whiteside ST, Goodbourn S. Signal transduction by subcellular localization (English) // Journal of Cell Science : journal. - The Company of Biologists , 1993. - April ( vol. 104 (Pt 4) ). - P. 949-955 . - PMID 8314906 .
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  33. Ity Laity JH, Lee BM, Wright PE Zinc Finger Proteins: New insights into structural and functional diversity (English) // Current opinion in structural biology: journal. - 2001. - February ( vol. 11 , no. 1 ). - P. 39—46 . - DOI : 10.1016 / S0959-440X (00) 00167-6 . - PMID 11179890 .
  34. ↑ Wolfe SA, Nekludova L., Pabo CO DNA recognition by Cys2His2 zinc finger proteins (English) // Annual review of biophysics and biomolecular structure : journal. - 2000. - Vol. 29 . - P. 183-212 . - DOI : 10.1146 / annurev.biophys.29.1.183 . - PMID 10940247 .
  35. ↑ Fichou, Y., Nectoux, J., Bahi-Buisson, N., Rosas-Vargas, H., Girard, B., Chelly, J., Bienvenu, T. The first missense influenza syndrome isoform. (English) // Neurogenetics: journal. - 2008. - November. - PMID 19034540 .
  36. ↑ Al-Quobaili F., Montenarh M. Pancreatic duodenal homeobox factor-1 and diabetes mellitus type 2 (review). (English) // Int J Mol Med. : journal. - 2008. - Vol. 21 (4) . - P. 399-404 . - PMID 18360684 .
  37. ↑ Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F., Monaco AP. A forkhead domain gene is mutated in a severe speech and language disorder. (English) // Nature: journal. - 2001. - Vol. 413 (6855) . - P. 519-523 . - PMID 11586359 .
  38. 2 1 2 Banerjee-Basu S., Baxevanis AD -PF subfamily of forkhead transcription factors. (English) // Proteins: journal. - 2004. - Vol. 54 (4) . - P. 639-647 . - PMID 14997560 .
  39. ↑ Ariffin H., Martel-Planche G., Daud SS, Ibrahim K., Hainaut P. Li-Fraumeni syndrome in Malaysian kindred. (Neopr.) // Cancer Genet Cytogenet .. - 2008. - Vol. 186 (1) . - p . 49-53 . - PMID 18786442 .
  40. ↑ Stegmaier P., Kel AE, Wingender E. Systematic DNA-binding domain classification factors (English) // Genome informatics. International Conference on Genome Informatics: journal. - 2004. - Vol. 15 , no. 2 - P. 276-286 . - PMID 15706513 . Archived June 19, 2013.
  41. ↑ Matys V., Kel-Margoulis OV, Fricke E., Liebich I., Land S., Barre-Dirrie A., Reuter I., Chekmenev D., Krull M., Hornischer K., Voss N., Stegmaier P ., Lewicki-Potapov B., Saxel H., Kel AE, Wingender E. TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes (eng.) // Nucleic Acids Res. : journal. - 2006. - Vol. 34 , no. Database issue . - P. D108-10 . - DOI : 10.1093 / nar / gkj143 . - PMID 16381825 .
  42. ↑ TRANSFAC ® database (Unc.) . The appeal date is August 5, 2007. Archived March 21, 2012.
  43. ↑ Qi Lei S. , Larson Matthew H. , Gilbert Luke A. , Doudna Jennifer A. , Weissman Jonathan S. , Arkin Adam P. , Lim Wendell A. Repurposing for Sequence-Specific Control of Generation Expression (eng.) // Cell. - 2013. - February ( vol. 152 , no. 5 ). - P. 1173-1183 . - ISSN 0092-8674 . - DOI : 10.1016 / j.cell.2013.02.022 . - PMID 23452860 .
  44. ↑ Farzadfard Fahim , Perli Samuel D. , Lu Timothy K. Tunable and Multifunctional Eukaryotic Transcription Factors Based on CRISPR / Cas (English) // ACS Synthetic Biology. - 2013. - 11 September ( vol. 2 , no. 10 ). - P. 604-613 . - ISSN 2161-5063 . - DOI : 10.1021 / sb400081r . - PMID 23977949 .
  45. ↑ Gilbert Luke A. , Larson Matthew H. , Morsut Leonardo , Liu Zairan , Brar Gloria A. , Torres Sandra E. , Stern-Ginossar Noam , Brandman Onn , Whitehead Evan H. , Doudna Jennifer A. , Lim Wendell A. , Weissman, Jonathan S. , Qi Lei, S. CRISPR-Mediated Modular Regulation // Cell. - 2013. - July ( t. 154 , № 2 ). - p . 442-451 . - ISSN 0092-8674 . - DOI : 10.1016 / j.cell.2013.06.044 . - PMID 23849981 .
  46. Rez Perez-Pinera Pablo , Kocak D Dewran , Vockley Christopher M , Adler Andrew F , Kabadi Ami M , Polstein, Lauren R , Thakore Pratiksha I , Glass Katherine A , Ousterout David G , Leong Kam Timothy E , Gersbach Charles A. RNA-guided gene activation by CRISPR-Cas9 – based transcription factors (English) // Nature Methods. - 2013. - 25 July ( vol. 10 , no. 10 ). - P. 973-976 . - ISSN 1548-7091 . - DOI : 10.1038 / nmeth.2600 . - PMID 23892895 .
  47. ↑ Purcell Oliver , Peccoud Jean , Lu Timothy K. Rule-Based Design of Synthetic Transcription Factors in Eukaryotes (eng.) // ACS Synthetic Biology. - 2014. - 3 January ( vol. 3 , no. 10 ). - P. 737-744 . - ISSN 2161-5063 . - DOI : 10.1021 / sb400134k . - PMID 24933274 .
Source - https://ru.wikipedia.org/w/index.php?title= Transcription Factors&oldid = 100910846


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