The Control of Gene Expression

The phenomenon of attenuation of translation of the trp operon in bacteria is provided as an example of posttranscriptional gene regulation. This mechanism, which is used by several amino acid biosynthetic operons, relies on alternative RNA secondary structures and on the coupling of transcription and translation in prokaryotes. The regulation of iron metabolism in animals is presented to show how RNA secondary structures can by bound specifically by proteins and thereby regulate translation. 

In preparation for studying this chapter, you should review Chapter 5, Sections 5.4 and 

and Chapter 28. Material on page 748 of the text describes the functional groups on DNA that can serve as determinants for specific interactions with proteins. Section 9.3.3 describes the binding of EcoRV endonuclease to DNA. These examples provide the principles by which the proteins described in this chapter could interact with specific sequences of DNA. 

When you have mastered this chapter, you should be able to complete the following objectives. 

Define gene expression and indicate the primary level of its regulation during expression of the genetic information. 

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Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

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). 

Since the discovery of the first histone demethylase in 2004, a number of demethy-lases have been identified and implicated in the control of gene expression programs and cell fate decisions. The cellular functions of histone demethylases are only beginning to be deciphered, but many of these enzymes have nevertheless been found to play biologically important roles. Histone demethylases are linked to the regulation of for example stem cell self-renewal, differentiation, proliferation and hormone-dependent responses. These processes are critical for development and cellular homeostasis and their deregulation is implicated in pathological disorders. 

CoweU, I.G. Repression versus activation in the control of gene expression (1994) Trends Biochem. Sd. 19, 38-42... 

The plasmid can be used, not only to transfer and express foreign genes in E. coli as with pBR322, but also to study the control of gene expression etc. Figures 5.28 and 5.29 show some of the procedures, each of which involves a number of steps ... 

The shuttling of some hnRNPs and their presence in the cytoplasm suggests that they play a role in the cytoplasmic metabolism of mRNA. It appears that the nuclear history of mRNAs influences their cytoplasmic fate, providing the cell with a new level for the control of gene expression (Matsumoto et al., 1998). The possibility exists that the shuttling hnRNPs are important players in this process. 

Hodges, P. and Scott, J. (1992) Apolipoprotein B mRNA editing a new tier for the control of gene expression. Trends Biochem. Sci. 17, 77-81. 

Westerhoff, H.V., Koster, J.G., van Workum,M. and Rudd, K.E. (1989) On the control of gene expression. In Control of Metabolic Processes. A. Comish-Bowden, M.L. Cardenas, eds. (New York Plenum Press), pp. 399 13, NATO ASl Series. 

Verdone L, Caserta M, Mauro ED. Role of histone acetyla- 74. tion in the control of gene expression. Biochem. Cell Biol. 2005 83 344-353. 

Steroid hormones can increase and decrease the level and/or activity of a large number of proteins in eukaryotes. Steroid hormones were first discovered in humans, where they play essential roles in development, differentiation, homeostasis, and endocrine therapies. However, current interest in steroid hormones is increasing because they constitute excellent model systems for examining the control of gene expression. Many human pathologies result from the inappropriate expression of protein(s). Thus, to treat disease states, it is critical to understand the normal processes governing how, when, and how much of the information encoded in the DNA of cells is transcribed to mRNAs and eventually into proteins, which perform most of the functions of cells. Steroid hormones provide excellent model systems with which to address these clinically relevant questions. 

DNA sequencing. The precise nucleotide sequence of a molecule of DNA can be determined. Sequencing has yielded a wealth of information concerning gene architecture, the control of gene expression, and protein structure. 

The Control of Gene Expression Requires Chromatin Remodeling... 

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