Topic 14: Regulation of Gene Expression in Eukaryotes

    Thousands of genes are present in each individual which each produce a gene product; however, the amount of gene product that each gene produces differs in different tissues and at different times in the same tissue.  Thus, the genes are regulated

1. Some important definitions:
   A. Inducible system: the amount of an enzyme synthesized increases when an inducer substance is
        present
   B. Repressible system: The amount of an enzyme synthesized decreases when a repressor substance is
        present
   C. Negative control: Expression occurs unless the gene is shut off by a regulatory molecule
   D. Positive control: Expression only occurs if the gene is turned on by a regulatory molecule
   E. Operon: A group of adjacent structural genes that are jointly controlled by a single regulatory site
   F. Polycystronic messenger: A single mRNA molecule that includes transcripts for more than one gene
   
   
2. The operon model (Jacob and Monod 1961)
   A. Involves the beta-galactosidase locus
       1. Converts the dissacharide, lactose, into the monosaccharides, glucose and galactose
   B. When no lactose is present in the medium, 3-5 molecules of this enzyme are present per cell; however,
       when lactose is present in the medium, thousands of molecules of this enzyme are present per cell
       1. This is an inducible system because the presence of an inducer substance (lactose) causes the cell
           to produce an increased level of an enzyme
   C. Two other enzymes, permease (which allows lactose to cross the cell membrane) and acetylase
        increase jointly with beta-galactosidase
   D. A polycistronic mRNA is produced which contains transcripts for all three structural genes
   E. There are three kinds of genes that are involved in this system:
       1. Structural genes (beta-galactosidase, permease, and acetylase genes) which code for proteins
       2. Operator gene (~30 base pairs) which regulates the activity of this operon
       3. Repressor gene (I) which produces a repressor protein which can bind to the substrate and also
           to the operator gene
   F.The repressor gene produces the repressor protein which can bind to the operator gene
       1. If the repressor protein is bound to the operator gene, transcription of the structural genes
           does not take place
       2. If the repressor protein is not bound to the operator gene, transcription of the structural genes
       takes place
   G. If lactose is absent, the repressor protein binds to the operator and transcription of the structural
       genes does not take place
   H. If lactose is present, a lactose molecule binds to the repressor protein and changes the configuration of
       the repressor protein so it is unable to bind to the operator gene, and the operator gene is transcribed
   I. The repressor protein is an allosteric protein, a protein which changes its conformation when it binds
       to another molecule (lactose)
   J. Regulation is at the transcriptional level
   K. This is an inducible system because transcription only occurs when lactose is present
   L. This operon is under negative control because genetic expression occurs unless it is shut off by the
       regulatory (repressor) molecule
   M. Two types of constitutive mutations (mutations in which the gene product is always produced) have
        been recovered
        1. Mutations in the repressor gene which produce a repressor protein which is unable to bind to the
            operator
        2. Mutations in the operator gene in which the repressor protein is unable to bind to the operator
   N. Jacob, Monod, and Lwoff were awarded the Nobel prize for this work in 1965
   O. The repressor molecule has been isolated, it is a protein
   
   
3. The tryptophan operon of E. coli, a repressible system
   A.E. coli growing in medium that contains no tryptophan produces enzymes that are necessary to
       synthesize tryptophan; however, when they are growing in medium with tryptopyhan, they do not
       produce these enzymes
       1. This is a repressible system because transcription does not occur when tryptophan is present
   B. There are five structural genes in this operon plus a promoter and a regulator gene
   C. For this operon, the regulator gene produces a repressor protein which only binds to the operon when
        it associates with the precursor, tryptophan; thus
       1. When tryptophan is absent, the repressor protein does not bind to the operator and the operon is
           transcribed
       2. When tryptophan is present, the tryptophan binds to the repressor protein changing the
           configuration of the repressor protein in such a way that it can now bind to the operator, and the
           operon is not transcribed
   D. It is under negative control because genetic expression occurs unless it is shut off by the repressor
           molecule

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Updated 11/28/00