Genes derepression

If this hypothesis is true, one would also expect to find poly-cis-C-carotene, -phytofluene, and -phytoene present in the fruit. Poly-cis induction appears to differ from the lycopene inducer in another respect. In addition to gene derepression, the lycopene inducers inhibit the cyclase(s), causing lycopene to accumulate at the expense of the cyclic carotenes. The accumulation of significant amounts of poly-cis-y-carotenes I and II indicates that the cyclase(s) is not inhibited by the poly-cis inducers and that their only apparent function is to derepress the recessive gene. 

Baniahmad, A., Ha, I., Reinberg, D., Tsai, S., Tsai, M -J., and O Malley, B W (1993) Interaction of human thyroid hormone receptor P with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc. Natl. Acad. Sci. USA 90, 8832-8836. 

To achieve overproduction of phenylalanine, the micro-organism should be derepressed at the pheA level and free of inhibition at the arcG level. Both genes are located on the chromosomal DNA of the micro-organism and, by means of amino add analogues such as p-fluoro-DL-phenylalanine, it is possible to make (phenylalanine) feedback resistant mutants of E.cdi (pheA and oroF mutants). The following procedure can be used ... 

Nijland, R., Veening, J.W. and Kuipers, O.P. (2007) A derepression system based on the Bacillus subtilis sporulation pathway offers dynamic control of heterologous gene expression. Applied and Environmental Microbiology, 73 (7), 2390-2393. 

Recent studies have demonstrated that overexpression of HDACl represses the tumor suppressors, p53 and von Hippel-Lindau (VHL), but induces the hypoxia-responsive genes, hypoxia inducible factor alpha (HIF-la) and vascular endothelial growth factor (VEGF) and increases angiogenesis. Conversely, HDAC inhibitors derepress the tumor suppressors, p53 and VHL, and repress HIF-la and VEGF [68, 69]. 

The importance of DNA methylation for normal genome function can also be shown by the finding that homozygous mutation of the DNMT gene results in embryonic lethality [46]. Thus, unwanted activation of certain genes by DNMT inhibitors may pose a risk, for example by derepression of proinvasive genes [47], which puts a caveat to those therapeutical approaches. 

The lowered concentration of bile acids returning to the liver by the enterohepatic circulation results in derepression of 7-a-hydroxylase, the rate-limiting enzyme for conversion of cholesterol to bile acids. This results in increased use of cholesterol to replace the excreted bile acids and lowering of hepatic cholesterol (mechanism VI in Fig. 23.2). Thus, similar to the statins, the ultimate actions of the bile acid-sequestering resins are up-regulation of transcription of the LDL receptor gene, increased hepatic receptor activity, and lowering of plasma LDL cholesterol (mechanism VII in Fig. 23.2). 

The transcription of nir and nor genes in P. stutzeri (Cuypers and Zumft, 1992, 1993) and P. aeruginosa (Zimmermann et al., 1991) would appear to be controlled in part by homologs of the Fnr protein of E. coli (Guest, 1992) which is a redox sensitive, transcriptional activator. Fnr boxes (binding sequences) are located upstream from norC, nirM and nirS. It is likely therefore that Fnr-like proteins participate in a regulatory mechanism which derepresses the synthesis... 

As well as induction of the synthesis of the apoprotein portion of cytochrome P-450, there is also induction of the synthesis of the heme portion. Clearly, it is also necessary to have an increased amount of heme if there is an increase in the amount of the enzyme apoprotein being synthesized. Thus, the rate-limiting step in heme synthesis, the enzyme 5-aminolaevulinate synthetase, is inducible by both phenobarbital and TCDD. This is the result of transcriptional activation of the gene, which codes for the S-aminolaevulinate synthetase. It may be that the decrease in the heme pool, which results from incorporation of heme into the newly synthesized apoprotein, leads to derepression of the gene and hence increased mRNA synthesis. The gene repression could be heme-mediated, or heme may modulate P-450 genes. 

---