Regulation of Gene Expression 2012

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RegulationofGeneExpression

AtifHassanKhirelsied,B.Sc.,M.Sc.,Ph.D.

DepartmentofBiochemistry

FacultyofMedicineInternationalUniversityofAfrica,Khartoum,Sudan


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Introductiontore ulationof eneex ression

Spatialregulation differentgenesareexpressedin

differentcelltypes.

Temporalregulation Differentgenesexpressedat

.

gna e y:

Environmentalstimuli Homeostasis(hormones,nutrient,etc.,)

Developmentanddifferentiation(growthfactors)


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unitofasetofclusteredgenes.

Anoperon includes:

structuralgenes,

codefortherelatedenzymesor

proteins.

regulatorygenes, codeforregulatorprotein(s)

control

elements

thataresitesontheDNAatwhichregu atorproteinsact.


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Istheincreaseingenetranscriptioninresponseto

thepresenceofaspecificsubstrate (inducer)inthemedium.

Exampleistheincreaseintranscriptionofthe alactosidase enewhenlactoseisthesolecarbon

source.


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R r i n

Istheswitchoff ofgeneexpressioninresponseto

signal.

WhenTrp issuppliedinthemedium,thebacteriastop

theexpressionofenzymesfortryptophansynthesis(repression).

energyformakingunnecessaryproteins


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LactoseOperon


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LactoseOperon


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MechanismofCatabolite Repression

Absenceofglucose

CAP ATP

Adenylcyclase

cAMP

i p o z y a

Active

Inactive

Galactosidase Permease Transacetylase

Maximumexpression


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MechanismofCatabolite Repression

Presenceofglucose

ATP

Adenylcyclase

CAPX

i p o z y a

Inactive

Galactosidase Permease Transacetylase


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RepressibleGenes Operon Model

Definition:Geneswhoseexpressionisturnedoffby

thepresenceofsomesubstance(corepressor)

Tr to han re resses the tr enes

orepressor s yp ca y een pro uc o e

pathway.


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TryptophanOperon


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TryptophanOperon

AbsenceofTryptophanCorepressor tryptophan

Absenceoftryptophan

Geneexpression

R P O E D C B AL

Inactiverepressor

5Proteins

Activatesrepressor

No eneex ression

R P O E D C B AL

PresenceofTryptophan

Negativecontrol

Inactiverepressor

(aporepressor)

Trp

(corepressor)


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Attenuation


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Attenuationinthetrp Operon ofE.coli


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INEUKARYOTES


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Genecontrolineukaryotes

Eukaryoticgeneexpressionisnecessaryfor

adaptationtochangesinenvironment.

Eukar otic ene ex ression ma be re ulated at

multiplelevels.


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GeneControlinEukaryotes

Eukaryoticgene

expressionmay

beregulatedatmultiplelevels


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GeneControlinEukaryotes

Eukaryoticgene

expressionmay

beregulatedatmultiplelevels


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Levelsofcontrolofgeneexpressionineukaryotes

Com artmentaion Chromatinremodelin Thechromatinstructure.

Transcri tionalre ulation.

GeneamplificationGenerearrangement.

Posttranscriptionalmodifications.

RNAtransport

RNAsplicing.RNAediting.

RNAstability Regulationoftranslation.

Posttranslationalmodification.

Proteintransport

Controlofproteinstability.


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Com artmentation .

Ineukaryoticcells,nucleus

separatesthetranscription

from translation .


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ChromatinStructure

Chromatinstructure nucleosome =DNAwrapped

aroundoctamer ofhistones.

Transcriptionally active(euchromatin),andinactive

.

eneamp cat on


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ChromatinStructure


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Chromatinremodeling.

affectstranscription.

Thepresenceofhistones andtheCpG methylation

affectsthetranscription.


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chargeanddisruptsthenucleosome structure.

Histone acetylase activityisassociatedwithTAFs.


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DNAmeth lation

DNAintheregulatoryregionsofimprintedgenesis

.

Enzymaticadditionofmethylgroupstothecarbon5

positionofaspecificcytosineresidue.


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Gene amplification

TherepeatedreplicationoftheDNAinalimitedportion.

transcription.


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Gene amplification

Exam lesofre ulationb eneam lificationinclude:

protein)drosophila.

Amplificationofgenesofdihydrofolate reductase

toresistmethotrexate (tumorcells).


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Generearrangement.

Thegenerationofantibodydiversityresultsfrom

segmentsduringthedevelopmentoftheBlymphocytes


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Somatic gene recombination in B cells

Kappa light chain gene rearrangement and generation ofk light-chain protein

Germline

Rearranged

VJjoining

chainDNA

PrimarRNA

Transcription

transcript

Polyadenylation,

RNAsplicing

m

Nascent

ol e tide

Translation

lightchain lightchain

S ti bi ti i B ll


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Heavy chain gene rearrangement and generation of heavy-chain proteins

Somatic gene recombination in B cells

Germline

HeavychainDNA

DJ oinin

VDJ

joining

Transcription

Rearranged

HchainDNA

Polyadenylation,

PrimarRNA

transcript

mRNA

Nascentpolypeptide

or heavychain heavy

chain heavy

chain


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Re ulationof enetranscri tion

ranscr p ona n a on s emos mpor an po n

forcontrolofeukaryoticgeneexpression.

Inbacteria,allgenesaretranscribedbythesameRNA

polymerase,whereasthreeRNApolymerasesfunctionineukaryotes.


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Re ulationof enetranscri tion

neu aryo es, e n erac on e ween epromo er

elementsandvarioustranscriptionfactorsprovides

e e c v eregu a on.

Tissue

specific

expression resultsfromtheactionof

enhancersorsilencer(repressors).


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DNAbin in r t in


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DNAbin in r t in

P i l l d h


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Promoterproximal elementsprecedethe

DifferentcombinationsofDNAbindingproteinsand

signa sequencesdeterminet etissuespeci ic

patternofgeneexpression.

P t t i ti l difi ti


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Posttranscriptionalmodifications

TissuespecificRNAmodificationsgeneratedifferentproteinsfromthesamegenesuchas:

1. Alternativesplicing

7different tropommyosin indifferenttissues.

2. Alternativepolyadenylation differentheavychainsofimmunoglobulinM(mIgM,sIgM).

3. Alternativepromoter intheratliverandpancreaticB

.

. ,

intoUAAintheapoBmRNAintheintestinalcells.


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Alternative promoter use

Differentialregulationoftheglucokinase (GK)geneisaccomplished

bytheuseoftissuespecificpromoters.


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Re ulationofRNATrans ort

TherateofmRNAtransporttocytoplasmprovidesanot erpoint orregu ation..

RegulationofRNAstability

Certainunstabletranscriptshavesequencese. . AUUUA that si nals for ra id de radation.


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Re ulationoftranslation

whichaffectstherecognitionofthecorrectAUG

evera s eps npro e nsyn es sareregu a e y

varioussignals.


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Re ulationdurin osttranslationalmodification

functioningofproteins.functioningofproteins.

SuchpostSuchposttranslationalmodificationsinclude:translationalmodificationsinclude:

G ycosy ationG ycosy ation

AcetylationAcetylation

FattyFattyacylationacylation

DisulfideDisulfidebondformationsbondformations


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Followingtranslationandprocessingproteinsare

trans ortedtotheirsiteofaction.

cell.


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1/2 .

ShortlivedproteinshavesequencesPESTthat

markproteinsfordegradation.

PEST= roline lutamate serine andthreonine.

Regulation of Gene Expression 2012

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