Controlling gene expression

Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

The ability of the leucine zipper proteins to form heterodimers greatly expands the repertoire of DNA-binding specificities that these proteins can display. As illustrated in Figure 10.19, for example, three distinct DNA-binding specificities could, in principle, be generated from two types of monomer, while six could be created from three types of monomer and so on. This is an example of combinatorial control, in which combinations of proteins, rather than individual proteins, control a cellular process. It is one of the most important mechanisms used by eucaryotic cells to control gene expression. 

In addition to affecting the efficiency of promoter utilization, eukaryotic cells employ alternative RNA processing to control gene expression. This can result when alternative promoters, intron-exon splice sites, or polyadenylation sites are used. Occasionally, heterogeneity within a cell results, but more commonly the same primary transcript is processed differendy in different tissues. A few examples of each of these types of regulation are presented below. 

Mierau, I. and Kleerebezem, M. (2005) 10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis. Applied Microbiology and Biotechnology, 68 (6), 705—717. 

JAKs and signal transducers and activators of transcription (STATs) are functionally analogous with IRS and PI3K. JAKs are physically associated with a cell surface receptor (e.g. for leptin, erythropoietin (EPO), growth factors or cytokines) STATs are free monomeric proteins within the cytosol but following phosphorylation by a JAK, individual proteins dimerize and then move into the nucleus of the cell where they control gene expression. 

Other Mechanisms for Controlling Gene Expression in Eukaryotes... 

Table 1-5-2 summarizes some of the mechanisms that control gene expression in eukaryotic cells. 

Phosphorylation of gene regulatory proteins such as CREB to control gene expression, usually over several hours. The typical result is to add more enzyme to the cell. CREB induces the phosphoenolpyruvate carboxykinase (PEPCK) gene. 

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. 

Koo BK, Stange DE, Sato T et al (2012) Controlled gene expression in primary Lgr5 organoid cultures. Nat Methods 9 81-83... 

Controls gene expression to maintain juvenile character... 

Genetic engineering nowadays allows us to control gene expression independent of the natural inducers of enzymatic activity and independent of the natural host that once harboured the enzyme. This is especially relevant since natural isolates are specialized in degradation of the educt, not synthesis of a product. Frequently, efficient degradation of the desired product is observed, which can be prevented by using a host different from the natural isolate. 

Stock, A. Ghen, T. Welsh, D. Stock, J. CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions. Proc. Natl. Acad. Sci. USA, 85, 1403-1407 (1988)... 

Colby, P. Davies, S. Kelly, D.J. Cuest, J.R. Andrews, S.C. Identification and characterization of a two-component sensor-kinase and response-regulator system (DcuS-DcuR) controlling gene expression in response to C4-dicarboxylates in Escherichia coli. J. BacterioL, 181, 1238-1248 (1999)... 

Why do we need vitamins Early clues came in 1935 when nicotinamide was found in NAD+ by H. von Euler and associates and in NADP+ by Warburg and Christian. Two years later, K. Lohman and P. Schuster isolated pure cocarboxylase, a dialyz-able material required for decarboxylation of pyruvate by an enzyme from yeast. It was shown to be thiamin diphosphate (Fig. 15-3). Most of the water-soluble vitamins are converted into coenzymes or are covalently bound into active sites of enzymes. Some lipid-soluble vitamins have similar functions but others, such as vitamin D and some metabolites of vitamin A, act more like hormones, binding to receptors that control gene expression or other aspects of metabolism. 

As of the early 1980s. numerous hypotheses have been formulated by molecular biologists and this fundamental discovery has stimulated a whole new line of research in many laboratories throughout the world. Some scientists have observed that the extra DNA cannot be accounted for simply upon the basis of evolutionary theories. The extra DNA may play a role in controlling gene expression. The complexity and current uncertainty of these hypotheses are beyond the scope of this book at this juncture in the research program. Perhaps the lopic will be better clarified at the lime of the next edition. Several of the references listed shed further insights. 

E. coli maintains all of its genes in a state where they can be turned on or turned off on short notice. The short messenger lifetime makes it possible to control gene expression from the transcription level. The lack of separate compartments for RNA and protein synthesis has fostered mechanisms where translation actually exerts a direct role on transcription. These are some of the special features that have influenced the evolution of regulatory systems in E. coli. 

Nguyen T, Sherratt PJ, Pickett CB. 2003. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43 233-260. 

Gossen, M., and Bujard, H. (1993) Anhydrotetracycline, a novel effector for tetracycline controlled gene expression systems in eukaryotic cells. Nucleic Acids Res., 21, 4411—4412. 

Nuyts, S., Landuyt, W., Lambin, P. and Anne, J. (2001) The use of radiation-induced bacterial promoters in anaerobic conditions a means to control gene expression in clostridium-mediated therapy for cancer. Radiation Res., 155, 716-723. 

Shin, M.K. (2000) Controlling gene expression in mice with tetracycline Application in pigment cell research. Pigment Cell Res., 13, 326-331. 

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