Regulatory transcription factors

We have learnt from the structures that the TBP/TATA complex is a nucleoprotein scaffold upon which other factors, such as TFIIA and TFIIB attach with high affinity through a combination of stereospecific and electrostatic interactions. TFIIB is positioned at the transcriptional start site, between the attachment sites for TBP and Pol II. On the other hand, TFIIA has no contacts with the DNA downstream of the TATA box and does not interact with the transcriptional start site and/or any of the components of the basal transcription machinery, all of which are located downstream of the TATA box. Thus, TFIIA and TFIIB can bind simultaneously, without mutual interference. Moreover, TFIIA is accessible to specific, signal-responsive regulatory transcription factors. Its location upstream of the TATA box also enables TFIIA to absorb and scavenge transcriptional inhibitors, making them ineffectual. 

To sum up for a gene to be transcribed, the chromatin wrapped in the nucleosome must become accessible to basic and signal-responsive regulatory transcription factors. 

Brugnera, E., O. Georgiev, F. Radke, R. Heuchel, E. Baker, G. Sutherland and W. Schaffner. Cloning, chromosomal mapping and characterisation of the human metal-regulatory transcription factor MTF-1. 

An additional cardinal regulatory mechanism of differential control of gene expression is chromatin structure. In eukaryotic cells, DNA is not naked but is packaged into nucleosomes, subunits of chromatin in which short tracts of DNA are wrapped around a core of histone proteins. As a consequence, accessibility of RNAP II and regulatory transcription factors to DNA is limited. More often than not, in the presence of a stable, inaccessible chromatin structure (heterochromatin), transcription is repressed, whereas the formation of an open accessible chromatin structure (euchromatin) is transcribed. ... 

The culture of hairy roots is an attractive alternative to the use of undifferentiated cell cultures to obtain secondary metabolites, since roots grow rapidly in hormone-free liquid medium, they are genetically stable and are differentiated cells potentially able to produce more secondary metabolites than undifferentiated cells. Hairy root cultures produce a broad spectrum of TIAs. Production of ajmalicine, serpentine, and catharanthine has been repeatedly reported by different authors, sometimes with levels superior to nontransformed root cultures (around 0.2-0A% DW) [49,50]. Production of vindoline has been surprisingly detected in hairy roots, in levels which are not so low (0.04-0.08% DW) [49, 51]. Very recent work with C. roseus hairy roots include elicitation treatments, overexpression of TIA genes, and regulatory transcription factors, but although vindoline is reported in some cases, the occurrence of anticancer TIAs was never reported, and vindoline levels were always below 0.08% DW [52-55]. 

The gene promoter is a nucleotide sequence in DNA near the start of a gene, consisting of regulatory elements to which transcription factors and RNA polymerase bind. This leads to activation of the gene promoter and transcription of the corresponding gene. 

Also, phosphorylation of Akt results in activation of sterol regulatory-element binding protein 1 (SREBP1), a key transcription factor involved in regulation of lipogenic enzymes. In addition, some of the effects of insulin on cell proliferation and survival may be explained by an Akt-dependent inhibition of apoptosis through phosphorylation and inactivation of proa-poptotic proteins (e.g., BAD, Caspase 9). 

Honda K, Takaoka A, Taniguchi T (2006) Type I interferon gene induction by Hie interferon regulatory factor family of transcription factors. Immunity 25 349-360... 

Activation of transcription by the binding of a transcription factor to a DNA-regulatory sequence. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

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