GENE REGULATION

1. GENE REGULATION • Virtually every cell in your body contains a complete set of genes • But they are not all turned on in every tissue • Each cell in your body expresses only a small subset of genes at any time • During development different cells express different sets of genes in a precisely regulated fashion

2. GENE REGULATION • Gene regulation occurs at the level of transcription or production of mRNA • A given cell transcribes only a specific set of genes and not others • Insulin is made by pancreatic cells

3. CENTRAL DOGMA • Genetic information always goes from DNA to RNA to protein • Gene regulation has been well studied in E. coli • When a bacterial cell encounters a potential food source it will manufacture the enzymes necessary to metabolize that food

4. Gene Regulation • In addition to sugars like glucose and lactose E. coli cells also require amino acids • One essential aa is tryptophan. • When E. coli is swimming in tryptophan (milk & poultry) it will absorb the amino acids from the media • When tryptophan is not present in the media then the cell must manufacture its’ own amino acids

5. Trp Operon • E. coli uses several proteins encoded by a cluster of 5 genes to manufacture the amino acid tryptophan • All 5 genes are transcribed together as a unit called an operon, which produces a single long piece of mRNA for all the genes • RNA polymerase binds to a promoter located at the beginning of the first gene and proceeds down the DNA transcribing the genes in sequence

6. Fig. 16.6

7. GENE REGULATION • In addition to amino acids, E. coli cells also metabolize sugars in their environment • In 1959 Jacques Monod and Fracois Jacob looked at the ability of E. coli cells to digest the sugar lactose

8. GENE REGULATION • In the presence of the sugar lactose, E. coli makes an enzyme called beta galactosidase • Beta galactosidase breaks down the sugar lactose so the E. coli can digest it for food • It is the LAC Z gene in E coli that codes for the enzyme beta galactosidase

9. Lac Z Gene • The tryptophane gene is turned on when there is no tryptophan in the media • That is when the cell wants to make its’ own tryptophan • E. coli cells can not make the sugar lactose • They can only have lactose when it is present in their environment • Then they turn on genes to beak down lactose

10. GENE REGULATION • The E. coli bacteria only needs beta galactosidase if there is lactose in the environment to digest • There is no point in making the enzyme if there is no lactose sugar to break down • It is the combination of the promoter and the DNA that regulate when a gene will be transcribed

11. GENE REGULATION • This combination of a promoter and a gene is called anOPERON • Operon is a cluster of genes encoding related enzymes that are regulated together

12. GENE REGULATION • Operon consists of • A promoter site where RNA polyerase binds and begins transcribing the message • A region that makes a repressor • Repressor sits on the DNA at a spot between the promoter and the gene to be transcribed • This site is called the operator

14. LAC Z GENE • E. coli regulate the production of Beta Galactocidase by using a regulatory protein called a repressor • The repressor binds to the lac Z gene at a site between the promotor and the start of the coding sequence • The site the repressor binds to is called the operator

16. LAC Z GENE • Normally the repressor sits on the operator repressing transcription of the lac Z gene • In the presence of lactose the repressor binds to the sugar and this allows the polymerase to move down the lac Z gene

17. LAC Z GENE • This results in the production of beta galactosidase which breaks down the sugar • When there is no sugar left the repressor will return to its spot on the chromosome and stop the transcription of the lac Z gene

20. GENE REGULATION • In eukaryotic organisms like ourselves there are several methods of regulating protein production • Most regulatory sequences are found upstream from the promoter • Genes are controlled by regulatory elements in the promoter region that act like one/off switches or dimmer switches

21. GENE REGULATION • Specific transcription factors bind to these regulatory elements and regulate transcription • Regulatory elements may be tissue specific and will activate their gene only in one kind of tissue • Sometimes the expression of a gene requires the function of two or more different regulatory elements

22. INTRONS AND EXONS • Eukaryotic DNA differs from prokaryotic DNA it that the coding sequences along the gene are interspersed with noncoding sequences • The coding sequences are called • EXONS • The non coding sequences are called • INTRONS

23. INTRONS AND EXONS • After the initial transcript is produced the introns are spliced out to form the completed message ready for translation • Introns can be very large and numerous, so some genes are much bigger than the final processed mRNA

24. INTRONS AND EXONS • Muscular dystrophy • DMD gene is about 2.5 million base pairs long • Has more than 70 introns • The final mRNA is only about 17,000 base pairs long

25. RNA Splicing • Provides a point where the expression of a gene can be controlled • Exons can be spliced together in different ways • This allows a variety of different polypeptides to be assembled from the same gene • Alternate splicing is common in insects and vertebrates, where 2 or 3 different proteins are produced from one gene