GENE REGULATION –PART 1

• Gene regulation is an important aspect of Molecular Biology
• It is the genetic control of gene regulation
• Deals with gene action and its control
• Genes coding for  a particular protein need not be active all the time
• They need to transcribe m-RNA only when a particular protein is required by the organism
• At other the gene could be switched off or kept away from transcription
• When needed the gene could be switched on or transcription could be resumed
• This is called regulation of gene action and many models have been proposed to explain
• Common among these is the Battery model for  Eukaryotes  and
• The Operon Model  that is appropriate for Prokayotes

Gene Battery Model

• Proposed By Roy John Britten and Eric. H. Davidson in 1969
• Explains regulation of Protein synthesis in eukaryotes
• The model proposes – four classes of gene sequences for control of gene action in  genomes of Eukarytoic multicellular organisms 
• They are
  • 1. Integrator gene
  • 2. Producer gene
  • 3. Receptor site and
  • 4. Sensor site
• Integrator gene: synthesizes activator for initiation of transcription
• Integrator needs to be activated by the sensor site
• Sensor site in turn is  activated by internal/external stimuli
• Producer gene is responsible for the production of the gene product i.e. Protein
• Receptor site is the site of binding of activator m-RNA to start the transcription
• This model is applicable to Eukaryotic genomes with split gene and is able to explain the presence of repetitive DNA
• Lacks experimental proof  hence not applied widely
• But in the modern context many of the molecular biology puzzles are taken into account in the model proposed

Operon Model 

• Proposed by Francois Jacob and Jacques Monad in 1961
• Explains gene regulation in Prokaryotic genomes where transcription and translation are simultaneous
• Can also be applied to monocistronic m-RNA in Eukaryotes
• Operons also found  in viruses like bacteriophages
• Postulates the presence of  a single Promoter gene that controls a gene cluster for a particular pathway

General Structure of  Operon

• An operon essentially consists of  two main Components  1.  Regulatory Genes  also called control genes and 2. Structural genes
• Regulatory Genes – generally present upstream of the structural genes and are involved in controlling transcription of structural genes.
• Regulatory genes may include an Inducer, Promoter and an Operator each having a special function
• Promoter is the site where the RNA polymerase binds to initiate transcription.
• Inducer is a sequence that is responsible for the synthesis of  repressor protein that controls transcription
• Operator is a site after the promoter where the  repressor binds to stop transcription
• Operator site has to be free of  repressor to initiate transcription of structural genes
• Several operons in E.coli have been studied and based on mode of regulation 2 important types of operons have been recognized

(Diagram provided in the last page as a scanned file)

LAC OPERON

• First studied in Escherichia coli
• Explains the control of genes involved in the uptake and utilization of Lactose by  E.coli
• Described by Jacob and Monad and has been experimentally proved based on the gene products of regulator and structural genes
• There are two parts
• Regulatory or Control genes
• Structural genes
• Regulatory genes are three regions commonly mentioned as i,p,o expanded as inducer, promoter and operator respectively
• Inducer gene need not necessarily be situated at the operon region.
• It can also be remotely present somewhere upstream  of the Operon
• Inducer is responsible for producing an repressor  protein that reversibly binds to Lactose
• Promoter is the region on the DNA to which the RNA polymerase enzyme binds to bring about transcription of the structural genes
• Operator is a part of the promoter to which  Lactose binds when lactose levels fall and so transcription is stopped
• Structural genes – In the Lac operon there are three  genes-Lac Z, Lac Y and Lac A
• Lac Z gene produces an enzyme called β-Galactosidase that breaks down Lactose to Glucose and Galactose
• Lac Y gene produces an enzyme called β-Galactoside permease that helps in uptake of Galactose into the cells
• Lac A gene  produces an enzyme called Galactoside acetyl transferase that helps in the assimilation of galactose by the cells

Mechanism of action of Lac Operon

• Lac Operon controls uptake and utilization of lactose
• Should be switched on when lactose is present
• Should be switched off when lactose is absent

When lactose is  PRESENT in the medium the following events take place:

• Inducer produces an i-m-RNA that produces a repressor protein which can bind at the operator region.
• Lactose binds to repressor  and prevents it from binding to operator
• RNA polymerase binds to Promoter and Transcription takes place
• Enzymes are formed
• Operon is switched  On

When lactose is  ABSENT  in the medium the following events take place:

• The repressor protein is not bound to Lactose
• Repressor binds to operator
• RNA polymerase is not able to move along the DNA
• Transcription is stopped
• Enzymes are not produced
• Operon is switched Off