Genetic regulatory mechanisms
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Genetic Regulatory Mechanisms. Control of Gene Expression. Transcriptional control Clustering of genes with related function Coordinate control of genes with related function Polycistronic mRNA. Inducible Genes - Operon Model.

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Genetic Regulatory Mechanisms

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Genetic regulatory mechanisms

Genetic Regulatory Mechanisms


Control of gene expression

Control of Gene Expression

  • Transcriptional control

  • Clustering of genes with related function

  • Coordinate control of genes with related function

  • Polycistronic mRNA


Inducible genes operon model

Inducible Genes - Operon Model

  • Definition: Genes whose expression is turned on by the presence of some substance

    • Lactose induces expression of the lac genes

    • An antibiotic induces the expression of a resistance gene

  • Catabolic pathways


Lactose operon

RegulatoryGene

Operon

DNA

i

p

o

z

y

a

m-RNA

Protein

-Galactosidase

Transacetylase

Permease

Lactose Operon

  • Structural genes

    • lac z, lac y, & lac a

    • Promoter

    • Polycistronic mRNA

  • Regulatory gene

    • Repressor

  • Operator

  • Operon

  • Inducer - lactose


Lactose operon1

Absence of lactose

z

y

a

i

p

o

Active

No lac mRNA

Presence of lactose

z

y

a

i

p

o

Inactive

-Galactosidase

Permease

Transacetylase

Lactose Operon

  • Inducer -- lactose

    • Absence

      • Active repressor

      • No expression

  • Presence

    • Inactivation of repressor

    • Expression

  • Negative control


Catabolite repression glucose effect

- glucose

Glucose added

Units of -galactosidase

+ glucose

Time (hr)

+ lactose

Catabolite Repression (Glucose Effect)

  • Definition: Control of an operon by glucose

  • Catabolic operons


Mechanism of catabolite repression

Adenyl cyclase

Absence of glucose

c-AMP

ATP

CAP

i

z

y

a

p

o

Active

Inactive

-Galactosidase

Permease

Transacetylase

Maximum expression

Mechanism of Catabolite Repression

  • c-AMP

  • CAP (CRP) protein

  • CAP-cAMP complex

    • Promoter activation

  • Positive control


Mechanism of catabolite repression1

Presence of glucose

CAP

Adenyl cyclase

X

ATP

Low level expression

z

y

a

i

p

o

Inactive

-Galactosidase

Permease

Transacetylase

Mechanism of Catabolite Repression

  • Glucose:cAMP

  • CAP (CRP) protein

  • No CAP-cAMP complex

    • No Promoter activation


Repressible genes operon model

Repressible Genes - Operon Model

  • Definition: Genes whose expression is turned off by the presence of some substance (co-repressor)

    • Tryptophan represses the trp genes

  • Biosynthetic pathways

    • Co-repressor is typically the end product of the pathway


Tryptophan operon

RegulatoryGene

Operon

A

B

L

R

P

O

E

D

C

Inactive repressor (apo-repressor)

5 Proteins

Tryptophan Operon

  • Structural genes

    • trp E, trpD, trpC trpB & trpA

    • Common promoter

  • Regulatory Gene

    • Apo-Repressor

      • Inactive

  • Operator

  • Leader

  • Operon

  • Co-repressor

    • Tryptophan


Tryptophan operon1

Absence of Tryptophan

A

B

L

R

P

O

E

D

C

Inactive repressor (apo-repressor)

5 Proteins

Presence of Tryptophan

A

B

L

R

P

O

E

D

C

No trp mRNA

Inactive repressor (apo-repressor)

Trp

(co-repressor)

Tryptophan Operon

  • Co-repressor -- tryptophan

    • Absence of tryptophan

      • Gene expression

  • Presence of tryptophan

    • Activates repressor

    • No gene expression

  • Negative control


Attenuation

L

DNA

3

4

P

O

1

2

E

RNA

ATG

TGA

3

4

1

2

2 trp codons

Attenuation

  • Definition: Premature termination of transcription

  • Leader region

    • Leader transcript

    • Translation start

    • Translation stop

    • Tryptophan codons


Attenuation1

4

1

2

3

UUUUUUU

3

2

UUUUUUU

4

1

Attenuation

  • Mutually exclusive mRNA secondary structure

    • region 1 : region 2

    • region 2 : region 3

    • region 3 : region 4

  • Coupled transcription and translation


Attenuation2

High tryptophanyl-t-RNA

Low tryptophanyl-t-RNA

3

3

4

4

1

1

2

2

ATG

TGA

ATG

TGA

UUUUUUU

2

1

4

2 trp codons

3

2 trp codons

3

2

UUUUUUU

4

1

No Attenuation

Attenuation

Attenuation


Regulation of enzyme activity

Regulation of Enzyme Activity

  • Feed back inhibition

  • Epigenetic modification

    • Post translational modifications

      • Phosphorylation/dephosphorylation

      • Adenylation/deadenylation


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