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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

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gene regulation
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
gene regulation2
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
central dogma
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
gene regulation4
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
trp operon
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
gene regulation7
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
gene regulation8
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
lac z gene
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
gene regulation10
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
gene regulation11
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
gene regulation12
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
lac z gene14
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
lac z gene16
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
lac z gene17
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
gene regulation20
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
gene regulation21
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
introns and exons
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
introns and exons23
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
introns and exons24
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
rna splicing
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