Transcription control

Regulatory proteins (transcription factors) are involved in controlling gene expression in all cells. These regulatory proteins bind to specific DNA sequences and thereby activate or inhibit the transcription of genes (Transcription control). The effects of transcription factors are usually reversible and are often controlled by ligands or by interconversion. 

The nomenclature for transcription factors is confusing. Depending on their mode of action, various terms are in use both for the proteins themselves and for the DNA sequences to which they bind. If a factor blocks transcription, it is referred to as a repressor otherwise, it is called an inducer. DNA sequences to which regulatory proteins bind are referred to as control elements. In prokaryotes, control elements that serve as binding sites for RNA polymerases are called promoters, whereas repressor-binding sequences are usually called operators. Control elements that bind activating factors are termed enhancers, while elements that bind inhibiting factors are known as silencers. 

The well-investigated lactose operon of the bacterium Escherichial coli can be used here as an example of transcriptional control. The lac operon is a DNA sequence that is simultaneously subject to negative and positive control. The operon contains the structural genes for three proteins that are required for the utilization of lactose (one transporter and two enzymes), as well as control elements that serve to regulate the operon. 

The interaction between the CAP-cAMP complex and DNA is shown in Fig. 4. Each subunit of the dimeric inducer (yellow or orange) binds one molecule of cAMP (red). Contact with the DNA (blue) is mediated by two recognition helices that interact with the major groove of the DNA. The bending of the DNA strand caused by CAP has functional significance. 

Transcription control is much more complex in eukaryotes (see p. 244). The number of transcription factors involved is larger, and in addition the gene activity is influenced by the state of the chromatin (see p. 238). 

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Regulatory regions are transcriptional control sequences, which consist of promoters, response elements, enhancers and possibly silencers, located upstream of the start site of transcription. The overall effect on gene transcription is a sum of the contributions of these elements and the activities of proteins recruited to these sites. Promoters are located immediately upstream of the start site and initiate transcription. They often contain tissue- or cell-specific elements if the gene is not ubiquitously expressed. Enhancers are positive regulatory elements which function independently of orientation and distance from the genes they regulate. 

The modulation of transcription nicely demonstrates how results of basic science can be translated into medical application. These few examples of drugs in successful use stimulate at the same time the intensive study of gaps in our understanding of transcriptional control, hoping to find new specific ways of interference. 

Kramer BP, Eischer C, Fussenegger M. BioLogic gates enable logical transcription control in mammalian cells. Biotechnol Bioeng 2004 87 478-84. 

DNA in transcriptionally active tegions is sensitive to nuclease attack some tegions are exceptionally sensitive and are often found to contain transcription control sites. 

Table 37-3. Some of the transcription control elements, their consensus sequences, and the factors that bind to them which are found in mammalian genes transcribed by RNA polymerase II. A complete list would include dozens of examples. The asterisks mean that there are several members of this family.

Transcription controls operate at the level of protein-DNA and protein-protein interactions. These interactions display protein domain modularity and high specificity. 

Ghromatin modifications are important in eukaryotic transcription control. 

Point mutations Protein folding Transcriptional control Frameshiftand nonsense mutations RNA processing Sickle cell disease P-Thalassemia P-Thalassemia P-Thalassemia... 

Induction of phase II enzymes, which conjugate reactive electrophiles and act as indirect antioxidants, appears to be the means for achieving protection against a variety of carcinogens in animals and humans. Transcriptional control of the expression of these enzymes is mediated, at least in part,... 

Cellular and extra-cellular environment regulatory genes transcription control... 

The novel mechanism of transcriptional control of the ferric citrate transport system via transmembrane signalling is also observed in Pseudomonas putida and probably also occurs in Pseudomonas aeruginosa. Synthesis of the PupB outer... 

Newton, R. et al. Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-lbeta. Biochem. Biophys. Res Commun. 237, 28, 1997. 

Dixon, D. A. et al. Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3 -untranslated region. J. Biol. Chem. 275, 11750, 2000. 

Crosa, J. H. (1997). Signal transduction and transcriptional and post transcriptional control of iron-regulated genes in bacteria, Microbiol. Mol. Biol. Rev., 61, 319-336. 

Thummel KE, Brimer C, Yasuda K, Thottassery J, Senn T, Lin Y, Ishizuka H, Kharasch E, Schuetz J, Schuetz E (2001) Transcriptional control of intestinal cytochrome P-4503A by 1-alpha, 25-dihydroxy vitamin D3. Mol Pharmacol 60 1399-1406. 

Auwerx, J., Schoonjans, K., Fruchart, J. C., and Staels, B. (1996). Transcriptional control of triglyceride metabolism Fibrates and fatty acids change the expression of the LPL and apo C-111 genes by activating the nuclear receptor PPAR. Atherosclerosis 124(Suppl.), S29-S37. 

Norris, T. L., Kingsley, R. A., and Bumler, A. J. (1998). Expression and transcriptional control of the Salmonella typhimurium Ip/fimbrial operon by phase variation. Mol. Microbiol. 29, 311-320. 

Doucas, V., The promyelocytic (PML) nuclear compartment and transcription control. Biochem Pharmacol, 2000, 60(8), 1197-201. 

The SCF and SCF-like complexes are multi-subunit RING-type E3s that represent the largest E3 family knotvn to date. This superfamily of E3s are involved in regulating cell-cycle progression, signal transduction pathways, transcriptional control, and multiple aspects of cell growth and development (reviewed in Ref. [50]). All members of this E3 superfamily contain two basic components, a member of the cullin protein family and a RING-domain protein. The cullin subumt serves as the... 

Among the several ubiquitin-like modifiers, SUMO is highly conserved from yeast to human and has been shown to regulate a variety of cellular functions such as nucleocytoplasmic transport, signal transduction, and transcriptional control... 

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