Transcription Factors| the role and structure of Transcription factor.

Transcription Factors 

“Transcription factors (TFs) are DNA-binding elements or proteins and are master regulators of gene expression”.

Transcription factors are the proteins that bind at the specific site on promoter region which is known as DNA-regulatory sequences (enhancers and silencers), localized in the 5-upstream region of targeted gene and hence regulate the expression of a gene, which means that they determine whether the gene going to transcribed into mRNA. Additionally, the activity of RNA polymerases is controlled by various TFs hence they activate or repress gene regulation. There is divers families of transcription have been identified that play a diverse role in cell division, growth, cell signaling pathways, differential gene regulation, and other mechanisms.  

                    

Figure 1: binding of TFs at promoter region to initiate the transcription.

Role of transcription factor

· Transcription factors play a very important role in response to various stimuli like environmental stress and signals from other cells and initiate a complex mechanism of cell signaling pathways to maintain the cellular environments. These intracellular signal transduction pathways, include the kinases PKA, MAPKs, JAKs, CDPK, and others which are simulated by cell-surface receptors or proteins.

· Many transcription factors, help to regulate the cell cycle and determine how large a cell will grow and when it will divide into two daughter cells. Those genes that are involved in the cell cycle are oncogenes (cancer-causing gene) and or tumor suppressor gene. TFs are involved in cancer by regulating the expression of oncogenes (cancer causing gene) and or in tumor suppressor gene

· Transcription factors function in the nucleus for the regulation of genes as they bind to the specific site at the promoter region which results in mRNA product and further production of protein.

· Many transcription factors are common to several cell types such as AP-1 and NF-κB, others are cell-specific which may determine the phenotype and have a role in development.

Structure of Transcription factor

 Typically, TFs have two most important regions: 1) DNA-binding motif and 2) a transcriptional regulatory motif.  

• DNA-binding domain (DBD)

DNA binding domain is the region of the TFs that recognize specific sequences of DNA (promotor or enhancer) localized in upstream proximity of promoter of many gene called cis-acting elements (transcription factor binding sites), Transcription Factors specifically recognize that binding site and thus regulating many downstream genes expression.

• Trans-activating domain (TAD) 

Trans-activating domain is the region that contains binding sites for other proteins such as transcription co-regulator. Trans-activation motif is the transcriptional regulatory domain and regulates the transcription of the adjacent gene. These binding sites are also called activation functions (AFs) or transcriptional regulatory motifs.   

• Signal-sensing domain (SSD) 

The signal-sensing domain is the exceptional motif that is responsible to senses external signals and, transmitting these signals to the rest of the transcription complex.

       

Figure 2: typical structure of TFs it shows DNA-binding domain DBD,  a transcriptional regulatory domain, and sign sensing domain.  

Transcription factor in plant

About 10% of the genome coding sequence in plants is devoted to encode TFs. Presently various transcription factors have been identified and reported in many plant species in Arabidopsis ~1500 TFs identified, in Oryza sativa 1611, in sorghum 2448, and others. Several databases of transcription factors are available which contain extensive information which enables us to elicit that data for a better understanding of TFs families in different species, signaling pathways, regulatory networks, corresponding binding sites, etc. These databases classified the Tfs into various families based on their own classification criteria, in plants about ∼72 families of transcription factors have been identified and classified, in a single plant Arabidopsis approximately 34 families are known. Some important gene families are named CBF/DREB (C-repeat binding factor/dehydration-responsive element binding), AP2/ERF (APETALA2/ethylene responsive factor), bHLH (basic helix-loop-helix), NAC (no apical meristem (NAM), WRKY, bZIP (basic leucine zipper), ZF-HD (zinc finger homeo-domain), MYB (myeloblastosis oncogene), MYC (myelocytomatosis oncogene). Some of the plant transcription factor database are PlantTFDB, STIFDB2, iTAK program /database, TreeTFDB, and TOBFAC.

Animal transcription factor 

Currently AnimalTFDB version 3.0 identified 125,135 TF genes out of which 80,060 transcription cofactor genes from 97 animal genome. To date around 941 TFs are identified in mice. Some of the important transcription factors include bZIP, Receptor zinc finger, myc, bHLH-ZIP, MyoD, homeobox transcription factor genes, Hox genes, Gallus gallus (Chicken), SOX2 present in yeast and animal, Grh/CP2 found in animal and fungi. The database of animal transcription is Animal Transcription Factor DataBase (AnimalTFDB).

Human transcription factor

In the human genome, approximately 10% of genes encode for transcription factors. In a study around 2800 proteins have been found that have DNA-binding domains of which 1600 function as transcription factors. Some of the transcription factors in humans are bZIP, C2H2 ZF, ADNP Homeodom,  sine oculis (SIX) homeobox family, C2H2-ZFs, HMG/Sox, Activating TF6 (ATF6A), Atonal bHLH transcription factor 7 (ATOH7 ), etc. Name of some human TFs databases is the Human TF–target regulations database, Silencer™ Human Transcription Factor siRNA Library, TF2DNA database. hTFtarget database which is a Comprehensive Database for Regulations of Human Transcription Factors and Their Targets.