Regulation of Gene Expression

• transcription

• posttranscription processes

• translation

• regulation of transcription

• regulation of posttranscription processes

• regulation of translation

• regulation of DNA transcription

• maturation of mRNA

• transport of RNA from nucleus + its localization in cytosol

• stability of mRNA

• regulation of translation

• posttranslational modifications

• controlling gene expression is often accomplished by controlling transcription initiation

• Regulatory proteins bind to DNA to either block or stimulate transcription —> depending on how they intercat with RNA polymerase

• Prokaryotic organism —> regulate gene expression in rensponse to their environment

• Eukaryotic cells —> regulate gene expression to maintain homeostatsis in the organism

• operon consists of regulatory region + structural genes

• regulatory region: promotor + operator

• RNA polymerase binds to promotor —> if not stopped proceeds over operon to transcribe the structural genes

• the repressor (regulatory protein) binds to the operator of the operon of the prokaryote —> transcription does not proceed = negative regulation

the lac operon contains genes for the use of lactose as an energy source

1) Regulatory region:

• CAP binding site

• promotor

• operator

2) Structural genes:

• lacZ

• lacY

• lacA

• CAP binds to the CAP binding site —> this promotes the RNA polymerase binding

• RNA Polymerase binds to promotor

• Repressor binds to operator —> block RNA polymerase

1) betta-galactosidase:

• hyrolyzed the disaccharide lactose into glucosa + galactose

2) Permease

• transmembrane symporter that pumps lactose into cell using a proton gradient in the same direction

3) betta-galactoside acetyltransferase (thiogalactoside transacetylase)

• acetylates galactose

all these proteins are produced when lactose is available to the cell but glucose is not.

—> lactose + NO glucose

• Permease —> LacY

• betta-galactosidase —> LacZ

• b-galactoside acetyltransferase —> LacA

• Glucose + NO lactose

• Lactose + NO glucose

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glucose + NO lactose = negative regulation

—> repressor (regulatory protein) is formed —> binds to the operator of the regulatory region of the lac operon

—> RNA polymerase moves but cant continue at operator —> Transcription is blocked by the binding of the repessor to the operator

lactose + NO glucose = induction of expression

• at presence of lactose + no glucose the repressor is formed + addictionally “Allolactose” is formed

• allolactose binds to the repressor —> conformtional change of repressor —> repressor can NOT bind to the operator

• RNA polymerase can continue to the coding region —> production of the polygenic mRNA

• polygenic mRNA translated into the 3 enzymes required for lactose metabolsim

before promotor lies the CAP binding site —> activated CAP needs to bind to CAP binding site so the RNA polymerase can bind to the promotor

low glucose in cell leads to production if cAMP —>if cAMP binds to the Non-active CAP —> CAP is activated

if there is no glucose —> phosphotransferase system (PTS)

• if there is NO glucose but lactose —> production of cAMP

• cAMP binds to inactive CAP —> form cAMP-CAP complexe —> positive regulation

• active CAP binds to the CAP binding site —> RNA Polymerase starts to move

• the repressor is inactive (no glucose)

• RNA polymerase can move —> catabolic induction of gene expression

• lactose + glucose —> there is no production of cAMP

• if there is no cAMP thre is no formation of the active cAMP-CAP complex —> does not bind to the CAP binding site

• RNA polymerase can Not bind to the promoter —> catabolic repression of gene expression

the trp operon encodes genes for the biosynthesis of tryptophan

• NOT expressed when the cell contains sufficient amounts of tryptophan

• trp operon is expressed when levels of tryptophan are low

the trp repressor protein

• trp repressor binds to the operator to block trancriprion

  
  

• binding of repressor to the operon requires a corepressor tryptophan —> low levels of tryptophan prevents the repressor from binding to the operon

• repressor (regulatory protein) can NOT bind to the operator

• RNA polymerase can continue —> enzymes needed for tryptophan synthesis are proced

• tryptophan binds to the regulatory protein (repressor) —> changes conformation of repressor so it can bind to the operator

• repressor binds to operator —> RNA polymerase can NOT continue

• trancription is blocked by the binding of the repressor to the operator

Transcription factors

• general transcription factors

• specific transcription factors

general transcriprion factors are required for transcription initiation

• required for binding RNA polymerase to DNA

• bind to the promotor region of the gene

specific transcription factors increase transcription in certain cells or in response to signals

many transcription factors are often found in the cell in an inactive state —> the activity of these factors is induced by:

• binding of ligand (an effector molecule)

• protein-protein interaction

• covalent modification (phosphorylation-dephosphorylation)

lipophilic hormones

• lipohilic hormone can simple diffuse through cell membrane

• lipohilic hormone either binds to cytoplasmic receptor (cytoplasm) which then transfers into nucleus or directly passes into nucleus and then binds to a nuclear receptor

• the formed hormone receptor complex dimerizes —> then binds to the hormone response element on DNA

• DNA is transcriped inro mRNA —> translation to protein