Control of Gene Expression

Genetic Regulation

• Every cell of a multicellular organism receives the same set of genetic information
  • Individual cells can exhibit different morphologies and behaviors
  • Differences are a result of the expression of a subset of genes in different cell types
    • Differential expression of selective genes determines cellular function

Complexity of Gene Expression

• Bacteria (procaryotes) have about 3000 genes that are required to row and respond to the environment.
• Eucaryotes must differentially express about 50,000 genes to grow, develop and reproduce
• Differences in complexity has resulted in the initial studies of gene regulation being conducted on procaryotic systems

Gene Regulation in Bacteria

• In bacteria genes of common function are clustered into functional units (Operons)
  • Inducible: "turned-on" when needed
  • Repressible: "turned-off" when no longer needed
• Operons are groups of genes that controlled by a single regulatory element

Inducible Operon

• Lac Operon is a cluster of genes that encode proteins involved in catabolism of lactose
  • This set of genes are not continuously expressed but are induced in the presence of a specific inducer
  • The inducer for this operon's expression is allolactose (a lactose derivative)

Lactose Operon (Lac Operon)

• Lac operon contains four contiguous genes:
  • First gene is regulatory gene referred to as a promoter which controls the transcription of the other genes
    • Binding site for RNA polymerase
• The remaining three genes are structural genes (Z,Y,A)which encode the amino acid sequence of proteins involved in the metabolism of lactose
• Expression of lac operon is controlled by a fifth gene: a regulatory gene ( I ) which produces a repressor protein

Lac Operon Functional Genes

• Z gene encodes an enzyme B-galactosidase
  • Breaks the disaccharide lactose into the monosaccharides of glucose and galactose
• Y gene encodes a membrane transport protein which moves lactose into the cell
• A gene encodes a transacylase, whose function within the lac operon is not understood

Jacob and Monad Model of Lac Operon Regulation

• Within the promoter gene there is a region called the operator (o)
  • The operator binds the protein product of the I gene preventing the binding of the RNA polymerase with the promoter
• In the presence of lactose (allolactose) an allosteric change occurs in the I protein and it's affinity for the operator region is lost
• Opening the possibility for the binding of RNA polymerase and the transcription (expression) of the structural genes

Repressible Operon

• Many operons are continuously active until their end-product exceeds the cellular demand
  • These operons are repressed ("turned-off") by a repressor proteins
    • Repressor proteins are inactive until activated by an allosteric change induced by the binding of a corepressor molecule
  • Activated repressor protein can bind to the operator and stop transcription

Positive versus Negative Control

• Negative control: a repressor molecule binds with the operator and stops transcription of the operon
  • Inducible and repressible operon are negatively controlled
• Positive control:control proteins bind to DNA and activates the operon
  • Transcriptional activator (TA)

Positive Control of Gene Expression

• Two examples of positive gene control are known.
• A chemical inducer binds to the TA activating it and allowing for interaction with the DNA facilitating transcription of the operon
• Catabolic gene-activator protein (CAP) regulates the metabolism of unusual nutrients
  • Inducer substance for CAP is cyclic AMP (cAMP)

Positive Control of Gene Expression

The second positive control strategy involvesa normally active control protein being inactivated by by the binding of a small molecule

• This strategy would reduce the transcription of the normally active genes
  • cAMP can similtaneously activate and inactivates genes for carbohydrarte metabolism
  • Glucosre versus Lactose as a carbon and energy source

Eucaryotic Gene Regulation

• Eucaryotic gene regulation is more complexthan in procaryotes due the size of the genome and the structure of the chromosome
  • Prior to transcription of a gene the DNA must be unpacked

Eucaryotic Chromosomes

• Eucaryotic chromosomes consist of DNA and proteins, the combination is referred to as chromatin
  • Chromosomal proteins consist of histone and non-histone proteins
    • Non-histone proteins are important in gene regulation
      • Diverse from organism to organsm, tissue to tissue and between developmental stages

Organization of Eucaryotic Chromosome

• Highly repetitive DNA representing about 10% of the genome is found in base sequences that are repeated thousands of times
  • Centromere and telomeres
• Moderately repetitive DNA comprises about 20% of the genome. Hundreds of copies
  • Tandem repeats: rRNAs
• Single copy (70%) of the genome
  • 1% of which is translated into proteins

Observation of Gene Transcription in Eucaryotes

• Stain of the chromosome distinguishes two separate regions
  • Euchromatin: weakly staining but active in gene transcription
  • Heterochromatin: strongly staining but inactive in gene transcription
• Lampbrush chromosomes and chromosomal puffs

Eucaryotic Gene Regulation

• Eucaryotes rely primarily on positive control mechanisms
  • Requires the involvement of transcription factors (TF)
    • TFs assist the RNA polymerase in binding with the promoter sequence
  • Two additional regulatory regions are involved
    • Inducer region:just upstream from the promoter
    • Enhancer region:1000s of nucleotides away

This page is maintained by James C. Pushnik: jpushnik@ecst.csuchico.edu

Last modified on 12/2/96