General Definition- Protein required for recognition by RNA polymerases of specific stimulatory sequences in eukaryotic genes.
In molecular biology, a transcription factor is a protein that binds DNA at a specific promoter or enhancer region or site, where it regulates transcription. Transcription factors can be selectively activated or deactivated by other proteins, often as the final step in signal transduction.
There are three classes of transcription factors:
- General transcription factors are involved in the formation of a preinitiation complex. The most common are abbreviated as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH. They are ubiquitous and interact with the core promoter region surrounding the transcription start site(s) of all class II genes.
- Upstream transcription factors are proteins that bind somewhere upstream of the initiation site to stimulate or repress transcription.
- Inducible transcription factors are similar to upstream transcription factors but require activation or inhibition.
Motifs found in transcription factors
- Helix-turn-helix (HTH) bind the major groove of the DNA.
- Zinc fingers function as structural platforms for DNA binding.
- Leucine zippers function in associating the transcription factors with each other.
- Basic-helix-loop-helix (bHLH) bind DNA with two alpha helices containing basic amino acid residues which are linked by a loop and are typically dimeric.
- G-quadruplex Motifs are recently being studied extensively for their role as a TF binding site
Examples of transcription factors
The Signal Transducers and Activator of Transcription (STAT) proteins regulate many aspects of cell growth, survival and differentiation. The transcription factors of this family are activated by the Janus Kinase JAK and dysregulation of this pathway is frequently observed in primary tumors and leads to increased angiogenesis and enhanced survival of tumors. Knockout studies have provided evidence that STAT proteins are involved in the development and function of the immune system and play a role in maintaining immune tolerance and tumor surveillance.
Function of STAT proteins
STAT proteins were originally described as latent cytoplasmic transcription factors that require phosphorylation for nuclear retention. The unphosphorylated STAT proteins shuttle between the cytosol and the nucleus waiting for its activation signal. Once the activated transcription factors reach the nucleus, they bind to a consensus DNA-recognition motif called gamma activated sites (GAS) in the promoter region of cytokine-inducible genes and activate transcription of these genes.
Activation of STAT proteins
Extracellular binding of cytokines induces activation of the intracellular [Janus kinase]? that phosphorylates a specific tyrosine residue in the STAT protein which promotes the dimerization of STAT monomers via their SH2 domain. The phosphorylated dimer is then actively transported in the nucleus via importin a/b and RanGDP complex. Once inside the nucleus the active STAT dimer binds to cytokine inducible promoter regions of genes containing gamma activated site (GAS) motif and activate transcription of this proteins. The STAT protein can be dephosphorylated by nuclear phosphatases which leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus by exportin crm1/RanGTP.