Transcriptional regulatory mechanisms

Corradi JP, Yang C, Darnell JC, Dalmau J, Darnell RB. A post-transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues. J Neurosci 1997 17(4) 1406-1415. 

Struhl K. Histone acetylation and transcriptional regulatory mechanisms. 1998. Cold Spring Harbor Laboratory, New York. 

There are most likely a number of diverse molecular pathways by which NO can alter gene expression, but in the case of MCP-1 this pathway has been partially elucidated. In human endothelial cells inhibition of NO synthesis has been shown to activate proteins capable of binding to oligonucleotides containing the NF-kB binding site (Zeiher etal., 1995), suggesting a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis. However, it cannot be excluded that NO also influences the activation of other transcription factors, such as AP-1, which has recently been characterized as an antioxidant-responsive factor (Meyer et al., 1993). Indeed, in in vitro gel-mobility assays the NO donor sodium nitroprusside, but no free NO, has been reported to S-nitrosylate the AP-1 moiety and inhibit its activity (Tabuchi et al., 1994). 

Sterner, D. E., and Berger, S. L. (2000). Acetylation of histones and transcription-related factors Microbiol. Mol. Biol. Rev. 64,435-459. Struhl, K. (1998). Histone acetylation and transcriptional regulatory mechanisms, Genes Dev. 12,599-606. 

Clearly, the control of gene expression at the transcriptional level is a key regulatory mechanism controlling carotenogenesis in vivo. However, post-transcriptional regulation of carotenoid biosynthesis enzymes has been found in chromoplasts of the daffodil. The enzymes phytoene synthase (PSY) and phytoene desaturase (PDS) are inactive in the soluble fraction of the plastid, but are active when membrane-bound (Al-Babili et al, 1996 Schledz et al, 1996). The presence of inactive proteins indicates that a post-translational regulation mechanism is present and is linked to the redox state of the membrane-bound electron acceptors. In addition, substrate specificity of the P- and e-lycopene cyclases may control the proportions of the p, P and P, e carotenoids in plants (Cunningham et al, 1996). 

The stability of phytoene desaturase and lycopene cyclase transcripts also influenced accumulation of carotenoids. Efforts in directed evolution of carotenogenic enzymes have also continued. Alternate approaches using systematic and combinatorial gene knockout targets have allowed for enhancement of carotenoid production in the absence of a priori assumptions of regulatory mechanisms. 

---