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 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
 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 Regulaion

• In addiion to sugars like glucose and lactose E.

coli cells also require amino acids
• One essenial 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
 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
Regulatory
Gene Operon

R P O L E D C B A

Inactive repressor
(apo-repressor) 5 Proteins
 RNA polymerase binds to a promoter
located at the beginning of the first gene
and proceeds down the DNA transcribing
the genes in sequence
 The tryptophane gene is turned on when
there is no tryptophan in the media
 the trp gene is a repressible gene (Genes
whose expression is turned off by the presence
of some substance (co-repressor))
 That is when the cell wants to make its’ own
tryptophan
Fig. 16.6
 Tryptophan Operon
Absence of Tryptophan

 Co-repressor -- R P O L E D C B A

tryptophan
 Absence of tryptophan
 Gene expression Inactive repressor
 Presence of tryptophan (apo-repressor) 5 Proteins
 Activates repressor
 No gene expression
Presence of Tryptophan
 Negative control
R P O L E D C B A

No trp mRNA
Inactive repressor Trp
(apo-repressor) (co-repressor)
 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 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 is an inducible gene ( Genes whose

expression is turned on by the presence of some
substance)
 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 break down
lactose
 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 REGULATION
 This combination of a promoter and a
gene is called an OPERON
 Operon is a cluster of genes encoding
related enzymes that are regulated together
Regulatory
Gene Operon

i p o z y a DNA

m-RNA

Protein

-Galactosidase Transacetylase
Permease
 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 GENE
Absence of lactose
 Normally the repressor
sits on the operator i p o z y a

repressing Active

transcription of the lac No lac mRNA

Z gene
 In the presence of
Presence of lactose
lactose the repressor
binds to the sugar and i p o z y a

this allows the

polymerase to move Inactive
down the lac Z gene
-Galactosidase Permease Transacetylase
 LAC Z GENE
Absence of lactose
 When there is no p y
i o z a
sugar left the Active
repressor will return No lac mRNA

to its spot on the

chromosome and
stop the transcription
of the lac Z gene
 Negative control
(bound repressor inhibits transcription)
 Catabolite Repression
(Glucose Effect)

- glucose
 Definition:

Units of galactosidase
Control of an
Glucose
operon by glucose added

+ glucose
 Catabolic operons
Time (hr)
+ lactose
 Mechanism of Catabolite Repression
Absence of glucose

 c-AMP
 CAP (CRP) Adenyl cyclase
CAP c-AMP ATP

protein
i p o z y a
 CAP-cAMP Active

complex
Inactive
 Promoter
-Galactosidase Permease Transacetylase
activation
Maximum expression

Positive control (bound activator facilitates trancription)

Mechanism of Catabolite Repression

 Glucose:cAMP Presence of glucose

 CAP (CRP) protein

Adenyl cyclase
 No CAP-cAMP
CAP X ATP

complex i p o z y a

 No Promoter
activation Inactive

-Galactosidase Permease Transacetylase

Low level expression

 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 on/off switches or dimmer
switches
 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