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Control of Gene Expression

Genetic Regulatory Mechanisms Dr. Jeffrey Patton Associate Professor Pathology, Microbiology, and Immunology USC-School of Medicine. Control of Gene Expression. Transcriptional control Clustering of genes with related function Coordinate control of genes with related function

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Control of Gene Expression

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  1. Genetic Regulatory MechanismsDr. Jeffrey PattonAssociate ProfessorPathology, Microbiology, and ImmunologyUSC-School of Medicine

  2. Control of Gene Expression • Transcriptional control • Clustering of genes with related function • Coordinate control of genes with related function • Polycistronic mRNA

  3. 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

  4. RegulatoryGene Operon DNA i p o z y a m-RNA Protein b-Galactosidase Transacetylase Permease Lactose Operon • Structural genes • lac z, lac y, & lac a • Promoter • Polycistronic mRNA • Regulatory gene • Repressor • Operator • Operon • Inducer - lactose

  5. Absence of lactose z y a i p o Active No lac mRNA Presence of lactose z y a i p o Inactive b-Galactosidase Permease Transacetylase Lactose Operon • Inducer -- lactose • Absence • Active repressor • No expression • Presence • Inactivation of repressor • Expression • Negative control

  6. - glucose Glucose added Units of ß-galactosidase + glucose Time (hr) + lactose Catabolite Repression (Glucose Effect) • Definition: Control of an operon by glucose • Catabolic operons

  7. CAP b-Galactosidase Permease Transacetylase Mechanism of Catabolite Repression Absence of glucose • c-AMP • CAP (CRP) protein • CAP-cAMP complex • Promoter activation • Positive control Adenyl cyclase c-AMP ATP i z y a p o Active Inactive Maximum expression

  8. CAP Mechanism of Catabolite Repression Presence of glucose • Glucose:cAMP • CAP (CRP) protein • No CAP-cAMP complex • No Promoter activation Adenyl cyclase X ATP z y a i p o Inactive b-Galactosidase Permease Transacetylase Low level expression

  9. 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

  10. 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

  11. 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 • Role of tryptophan

  12. L DNA 3 4 P O 1 2 E RNA AUG UGA 3 4 1 2 2 trp codons Attenuation • Definition: Premature termination of transcription • Leader region • Leader transcript • Translation start • Translation stop • Tryptophan codons

  13. 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

  14. High tryptophanyl-t-RNA Low tryptophanyl-t-RNA 3 3 4 4 1 1 2 2 AUG UGA AUG UGA UUUUUUU 2 1 4 2 trp codons 3 2 trp codons 3 2 UUUUUUU 4 1 No Attenuation Attenuation Attenuation

  15. Regulation of Enzyme Activity • Feed back inhibition • Epigenetic modification • Post translational modifications • Phosphorylation/dephosphorylation • Adenylation/deadenylation

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