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Mechanisms for Controlling Eukarytotic Gene Expression.

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Introduction

Mechanisms for Controlling Eukarytotic Gene Expression. Every cell in a multicellular organism (eukaryote) has the potential to express every gene in the genotype. However for proper development and functioning certain cells must express only certain genes at appropriate times. Therefore the expression of such genes must be tightly regulated. Eukaryotes find many ways of controlling gene expression but they fall mainly into these three categories: transcription, RNA processing and Translation. In some cases regulation can depend on the DNA itself, the position of genes on a chromosome and their respective frequency. In other cases the proteins that bind to the DNA can make genes more or less available for transcription. The processing and transcription of the pre-mRNA can be regulated. Transport of the pre-mRNA into the cytoplasm, its translation into protein can be controlled. Finally, once the protein itself is made, its structure can be modified, thereby affecting its activity. All of these methods for control will be explained in turn according to the three categories explained above. Transcriptional Control Transcription is the process of creating a complementary strand of mRNA (messenger RNA) from the double stranded DNA precursor. This mRNA is the intermediate between the DNA and the amino acids coding for the protein. Both liver cells and brain cells express certain " housekeeping" proteins, for example those used in glycolysis, but they also need to express specific proteins concerned with the nature of the cell e.g. digestive enzymes. Obviously not all cells express these genes and so transcriptional control is the first step in saying what actual genes are used in the first place. ...read more.

Middle

Or it can act conversely to activator proteins binding to sites upstream and disrupting the complex. A diagram of the position of the elements in the transcription complex: Unattributed Internet site. How do all these different elements actually regulate transcription? The answer seems that all genes in most tissues can transcribe a small amount of RNA. But the right combination of all the above factors determines the maximum rate of transcription. For example in the immature red blood cells of bone marrow, which make a large amount of the protein �-globin, the transcription of globin genes is stimulated by the binding of seven inducers and six activators. By contrast in white blood cells, in the same bone marrow, these regulatory proteins are not made and they do not bind to their sites adjacent to the �-globin genes; consequently these genes are hardly transcribed at all. The Binding Of Proteins To DNA. The complexity of regulation however starts even before the creation of the initiation complex. The activation of transcription factors is the first step. This can be done in two ways, depending on the type of gene expressed. Control via lipid soluble hormones. This is gene regulation on an extra cellular level. Lipid soluble hormones, such as steroids are created by other cells and packaged off into the bloodstream. Because they are non-polar molecules they are able to pass through the target cells membrane and into its cytoplasm. Once inside they bind to certain TFs via zinc fingers (explained shortly) ...read more.

Conclusion

Translational and Posttranslational Control Once the mRNA has been cut down to the appropriate size it is ready to code for a protein by attaching itself to a ribosome. However the amount of free mRNA in the cell can be regulated by binding it to a protein in a negative feedback fashion in some cases to stop a cell overproducing a certain protein. For example the translational repressor protein that binds to ferritin mRNA when iron levels are too high in the blood. The process of translation can be controlled. One method of control is the use of capping at the 5' end of the mRNA, via a modified guanosine residue. mRNA's that do not have a modified cap are not translated. This modification of the normal guanosine cap can occur at any time during development making the mRNA active. The final method for control in gene expression regards the modification of proteins after synthesis, such as glycosylation or phosphorylation. Also their lifespan in the cell is important. For example transcriptional inducers must only be present when needed otherwise the gene would always be on. A small protein called ubiquitin is used in the breakdown of proteins. It collects around the surface of the protein and attracts a large complex of proteases which catalyse its breakdown. Even single celled organisms such as yeasts have many of these complex regulation mechanisms. In multicellular organisms these mechanisms must also co-ordinate the activities of different cells and tissues. Gene regulation is all about the expression of genotype into phenotype. This is most impressive when looking at the development of a single cell into a complex organism. ...read more.

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