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CONTROL OF GENE EXPRESSION
Control of Gene Expression
INTRODUCTION:
By gene expression we mean the transcription of a gene into mRNA and its subsequent
translation into protein.
 Gene expression is primarily controlled at the level of transcription, largely as a result of
binding of protein to specific sites on DNA.
 In 1965 Francois Jacob and Jacques Monod, shared the Nobel prize in medicine for their
work supporting the idea that control of enzyme levels in cells is regulated by transcription
of DNA.
 Occurs through regulation of transcription, which can be either induced or repressed.
 These researchers proposed that production of the enzyme is controlled by an "operon,"
which consists a series of related genes on the chromosome consisting of an operator, a
promoter, a regulator gene, and structural genes.
The structural genes contain the code for the proteins
products that are to be produced.
The promoter gene doesn't encode anything; it is simply a
DNA sequence that is initial binding site for RNA polymerase.
The operator gene is also non-coding; it is just a DNA
sequence that is the binding site for the repressor.
The regulator gene codes for synthesis of
a repressor molecule that binds to the operator and blocks
RNA polymerase from transcribing the structural genes.
The operator gene is the sequence of non-transcrible DNA that
is the repressor binding site.
There is also a regulator gene, which codes for the synthesis of
a repressor molecule hat binds to the operator
Inducible Transcription
For example: The bacterium E. coli has three genes that
encode for enzymes that enable it to split and metabolize
lactose (a sugar in milk).
 The promoter is the site on DNA where RNA polymerase binds
in order to initiate transcription.
However, the enzymes are usually present in very low
concentrations,
Because their transcription is inhibited by a repressor protein
produced by a regulator gene.
Conti….
 The repressor protein binds to the operator site and inhibits
transcription.
However, if lactose is present it will bind to the repressor protein
and inactivate it,
 Effective removing the blockade and enabling transcription of the
messenger RNA needed for synthesis of these genes
Repressible Transcription:
For example :E. coli need the amino acid tryptophan, and the
DNA in E. coli also has genes for synthesizing it.
These genes generally transcribe continuously since the
bacterium needs tryptophan.
However, if tryptophan concentrations are high, transcription is
repressed (turned off) by binding to a repressor protein
and activating it as below
Control of Gene Expression in Eukaryotes
Eukaryotic cells have similar mechanisms for control of gene
expression, but they are more complex.
 For example, that prokaryotic cells of a given species are all
the same
 But most eukaryotes are multicellular organisms with many cell
types, so control of gene expression is much more complicated.
Gene expression in eukaryotic cells is controlled by a number
of complex processes which are summarized by the following
list.
After fertilization, the cells in the embryo become increasingly specialized,
largely by turning on some genes and turning off many others.
Some cells in the pancreas, for example, are specialized to synthesize and
secrete digestive enzymes
Pancreatic cells (β-cells in the islets of Langerhans) are specialized to
synthesis and secrete insulin.
Each type of cell has a particular pattern of expressed genes. This
differentiation text annotation indicator into specialized cells occurs largely
as a result of turning off the expression of most genes in the cell;
 Mature cells may only use 3-5% of the genes present in the cell's nucleus.
Similar to the operons described above for prokaryotes, eukaryotes
also use regulatory proteins to control transcription
But each eukaryotic gene has its own set of controls. In addition,
there are many more regulatory proteins in eukaryotes and the
interactions are much more complex.
Before the mRNA leaves the nucleus, the introns are removed from
the transcript by a process called RNA splicing (see graph below), and
extra nucleotides are added to the ends of the transcript; these non-
coding "caps" and "tails" protect the mRNA from attack by cellular
enzymes and aid in recognition by the ribosomes.
Variation in the longevity of mRNA provides yet another opportunity for control of
gene expression.
Prokaryotic mRNA is very short-lived, but eukaryotic transcripts can last hours, or
sometimes even weeks (e.g., mRNA for hemoglobin in the red blood cells of birds).
The process of translation offers additional opportunities for regulation by many
proteins.
 For example, the translation of hemoglobin mRNA is inhibited unless iron-
containing heme is present in the cell.
There are also opportunities for "post-translational" controls of gene expression in
eukaryotes. Some translated polypeptides (proteins) are cut by enzymes into
smaller, active final products.
 As in the figure below which depicts post-translational processing of the hormone
insulin. Insulin is initially translated as a large, inactive precursor; a signal sequence
is removed from the head of the precursor, and a large central portion (the C-
chain) is cut away, leaving two smaller peptide chains which are then linked to each
other by disulfide bridges. The smaller final form is the active form of insulin.
Gene expression can also be modified by the breakdown of the
proteins that are produced.
For example, some of the enzymes involved in cell metabolism are
broken down shortly after they are produced; this provides a
mechanism for rapidly responding to changing metabolic demands.
Gene expression can also be influenced by signals from other cells.
There are many examples in which a signal molecule (e.g., a
hormone) from one cell binds to a receptor protein on a target cell
and initiates a sequence of biochemical changes (a signal
transduction pathway) that result in changes within the target cell.
 These changes can include increased or decreased transcription as
in the figure below.
RNAi :
The RNA Interference system (RNAi) is another
mechanism by which cells control gene expression.
 Shutting off translation of mRNA.
 RNAi can be used to shut down translation of viral
proteins when a cell is infected by a virus.
 The RNAi system also has the potential to be exploited
therapeutically.
• Some RNA virus will invade cells and introduce double-
stranded RNA
• Which use the cells machinery to make new copies of
viral RNA and viral proteins.
• The cell's RNA interference system (RNAi) can prevent
the viral RNA from replicating.
RNAi

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Control of gene expression ppt

  • 1. CONTROL OF GENE EXPRESSION
  • 2. Control of Gene Expression INTRODUCTION: By gene expression we mean the transcription of a gene into mRNA and its subsequent translation into protein.  Gene expression is primarily controlled at the level of transcription, largely as a result of binding of protein to specific sites on DNA.  In 1965 Francois Jacob and Jacques Monod, shared the Nobel prize in medicine for their work supporting the idea that control of enzyme levels in cells is regulated by transcription of DNA.  Occurs through regulation of transcription, which can be either induced or repressed.  These researchers proposed that production of the enzyme is controlled by an "operon," which consists a series of related genes on the chromosome consisting of an operator, a promoter, a regulator gene, and structural genes.
  • 3. The structural genes contain the code for the proteins products that are to be produced. The promoter gene doesn't encode anything; it is simply a DNA sequence that is initial binding site for RNA polymerase. The operator gene is also non-coding; it is just a DNA sequence that is the binding site for the repressor. The regulator gene codes for synthesis of a repressor molecule that binds to the operator and blocks RNA polymerase from transcribing the structural genes.
  • 4. The operator gene is the sequence of non-transcrible DNA that is the repressor binding site. There is also a regulator gene, which codes for the synthesis of a repressor molecule hat binds to the operator
  • 5. Inducible Transcription For example: The bacterium E. coli has three genes that encode for enzymes that enable it to split and metabolize lactose (a sugar in milk).  The promoter is the site on DNA where RNA polymerase binds in order to initiate transcription. However, the enzymes are usually present in very low concentrations, Because their transcription is inhibited by a repressor protein produced by a regulator gene.
  • 6. Conti….  The repressor protein binds to the operator site and inhibits transcription. However, if lactose is present it will bind to the repressor protein and inactivate it,  Effective removing the blockade and enabling transcription of the messenger RNA needed for synthesis of these genes
  • 7.
  • 8. Repressible Transcription: For example :E. coli need the amino acid tryptophan, and the DNA in E. coli also has genes for synthesizing it. These genes generally transcribe continuously since the bacterium needs tryptophan. However, if tryptophan concentrations are high, transcription is repressed (turned off) by binding to a repressor protein and activating it as below
  • 9.
  • 10. Control of Gene Expression in Eukaryotes Eukaryotic cells have similar mechanisms for control of gene expression, but they are more complex.  For example, that prokaryotic cells of a given species are all the same  But most eukaryotes are multicellular organisms with many cell types, so control of gene expression is much more complicated. Gene expression in eukaryotic cells is controlled by a number of complex processes which are summarized by the following list.
  • 11. After fertilization, the cells in the embryo become increasingly specialized, largely by turning on some genes and turning off many others. Some cells in the pancreas, for example, are specialized to synthesize and secrete digestive enzymes Pancreatic cells (β-cells in the islets of Langerhans) are specialized to synthesis and secrete insulin. Each type of cell has a particular pattern of expressed genes. This differentiation text annotation indicator into specialized cells occurs largely as a result of turning off the expression of most genes in the cell;  Mature cells may only use 3-5% of the genes present in the cell's nucleus.
  • 12. Similar to the operons described above for prokaryotes, eukaryotes also use regulatory proteins to control transcription But each eukaryotic gene has its own set of controls. In addition, there are many more regulatory proteins in eukaryotes and the interactions are much more complex. Before the mRNA leaves the nucleus, the introns are removed from the transcript by a process called RNA splicing (see graph below), and extra nucleotides are added to the ends of the transcript; these non- coding "caps" and "tails" protect the mRNA from attack by cellular enzymes and aid in recognition by the ribosomes.
  • 13.
  • 14. Variation in the longevity of mRNA provides yet another opportunity for control of gene expression. Prokaryotic mRNA is very short-lived, but eukaryotic transcripts can last hours, or sometimes even weeks (e.g., mRNA for hemoglobin in the red blood cells of birds). The process of translation offers additional opportunities for regulation by many proteins.  For example, the translation of hemoglobin mRNA is inhibited unless iron- containing heme is present in the cell. There are also opportunities for "post-translational" controls of gene expression in eukaryotes. Some translated polypeptides (proteins) are cut by enzymes into smaller, active final products.  As in the figure below which depicts post-translational processing of the hormone insulin. Insulin is initially translated as a large, inactive precursor; a signal sequence is removed from the head of the precursor, and a large central portion (the C- chain) is cut away, leaving two smaller peptide chains which are then linked to each other by disulfide bridges. The smaller final form is the active form of insulin.
  • 15.
  • 16. Gene expression can also be modified by the breakdown of the proteins that are produced. For example, some of the enzymes involved in cell metabolism are broken down shortly after they are produced; this provides a mechanism for rapidly responding to changing metabolic demands. Gene expression can also be influenced by signals from other cells. There are many examples in which a signal molecule (e.g., a hormone) from one cell binds to a receptor protein on a target cell and initiates a sequence of biochemical changes (a signal transduction pathway) that result in changes within the target cell.  These changes can include increased or decreased transcription as in the figure below.
  • 17.
  • 18. RNAi : The RNA Interference system (RNAi) is another mechanism by which cells control gene expression.  Shutting off translation of mRNA.  RNAi can be used to shut down translation of viral proteins when a cell is infected by a virus.  The RNAi system also has the potential to be exploited therapeutically.
  • 19. • Some RNA virus will invade cells and introduce double- stranded RNA • Which use the cells machinery to make new copies of viral RNA and viral proteins. • The cell's RNA interference system (RNAi) can prevent the viral RNA from replicating. RNAi