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Regulation of gene expression in prokaryotes and eukaryotes.

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Introduction

Regulation of gene expression in prokaryotes and eukaryotes For a bacterium, it would be wasteful to transcribe all its genes at the same time- for example, it would be silly for a bacterium to produce enzymes for the synthesis of an amino acid, if it was readily available from its environment. And so bacterium have evolved a number of mechanisms for regulating gene expression. Potentially, there are 3 sites of control: * by changing gene transcription * by changing mRNA turnover time * by changing the rate of translation The mechanisms that I wish to discuss are those involving the regulation of gene transcription. Prokaryotic genomes differ to eukayotic genomes, in various manners, for example, eukaryotic genomes contain significantly more non-coding sequences than do those of prokaryotes. Also, many bacterial genes exist as operons, the genes are coordinately arranged to give proteins with related functions. Operons may be inducible, or repressible, and include the lac operon (an inducible operon, with genes coding for enzymes needed for lactose metabolism) and the trp operon (a repressible operon with genes coding for ezymes involved in the biosynthesis of tryptophan). The lac operon There are 3 genes in this operon (lac Z, Y and A), and, transcribed sequentially into a single mRNA strand, they code for enzymes needed by E.Coli for lactose metabolism. Although there is always a basal transcrption rate for this operon, in the presence of lactose, the transcription rate increase rapidly. ...read more.

Middle

And a final method is by regulation by alternative sigma factors. RNA polymerase is the enzyme responsible for DNA transcription, and in bacteria this enzyme is composed of 5 polypeptide subunits, one of which is called sigma factor (?). Sigma factor is responsible for initiating transcription by recognizing bacterial promoter DNA sequences. Bacteria such as E.coli retain the ability to make alternative sigma factors, that recognize different sets of promoters- resulting in RNA polymerase transcribing different sets of genes. Since environmental conditions can dictate changes in the type of sigma factor used, this is a way of regulating gene expression. The most common factor used by E.coli is ?70, although alternative sigma factors may be seen under different conditions, such as: * heat shock- if E.coli is exposed to high temperatures, it begins to transcribe a set of 17 proteins that are necessary for its continued survival in the harsh environment. The alternative factor ?32 is produced, and this recognizes promoters for the otherwise-not-expressed heat shock genes. * Sporulation in Bacillus subtilis- B.subtilis undergoes sporulation as a response to adverse environmental conditions. Sporulation involves a major change in the cell's usual activity, requiring production of specific proteins not usually expressed and shut-down of the protein usually synthesised. The bacteria achieves this through alternative sigma factors. * Bacteriophage ? factors- phages are viruses that attack bacteria by attaching to the bacterial surface and injecting their DNA core into the host cell, and reproducing. ...read more.

Conclusion

Transcription factors may also bind to sequence elements known as enhancers, and these are found at long distances from the gene. It was originally thought that enhancers were separate to promoter-UREs, because they: * can activate transcription over long distances * can be found upstream/downstream of the gene being controlled * are active in any orientation with respect to the gene But it is now accepted that enhancers and promoter-UREs show strong similarities physically and functionally. So how do transcription factors interact with the DNA? Well, transcription factors consist of 2 domains- a DNA-binding domain, and an activation domain, and some transcription factors operate as dimers, and so have dimerization domains. DNA-binding domains There are 3 main types of binding domain: * HELIX-TURN-HELIX - 2 alpha-helices separated by a beta-turn. The recognition helix binds to the DNA by making contact through the major groove * ZINC FINGERS- 2 beta-strands and an alpha-helix that also makes contact through the major groove. * BASIC DOMAINS- found in some transcription factors- ususally with leucine zipper or helix-loop-helix. Dimerization domains There are 2 types: * LEUCINE ZIPPERS- * HELIX-LOOP-HELIX- 2 alpha-helices separated by a nonhelical loop. The helix-loop-helix dimerization domain is found in the MyoD family of transcription factors that regulate gene expression in developing muscl cells. Activation domains There are no motifs that characterize activation domains, although they can be divided into 3 types: * those containing a lot of acidic amino acids * those containing a lot of glutamine * those containing a lot of proline ...read more.

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