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Control of Gene Expression

Chapter 16


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Controlling gene expression is often

accomplished by controlling transcription

initiation.

Regulatory proteins bind to DNA to

either block or stimlate transcription!

depending on ho" they interact "ith #NA

polymerase.


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$rokaryotic organisms reglate gene

expression in response to their

en%ironment.

Ekaryotic cells reglate gene expression

to maintain homeostasisin the organism.


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#eglatory $roteins

Gene expression is often controlled by

reglatory proteins binding to specific DNA

se&ences.

' reglatory proteins gain access to the

bases of DNA at the major groove

' reglatory proteins possess DNA-

binding motifs


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#eglatory $roteins

DNA(binding motifs are regions of

reglatory proteins "hich bind to DNA

'helix-turn-helix motif

' homeodomain motif

' zinc finger motif

' leucine zipper motif


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)elix(*rn()elix +otif


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)omeodomain +otif


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,inc -inger +otif


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ecine ,ipper +otif


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$rokaryotic #eglation

Control of transcription initiation can be/

' positive control' increases

transcription "hen activatorsbind DNA

' negative control' redces

transcription "hen repressorsbind to

DNA reglatory regions called

operators


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$rokaryotic cells often respond to theiren%ironment by changes in geneexpression.

Genes in%ol%ed in the same metabolicpath"ay are organi0ed in operons.

ome operons are induced "hen the

metabolic path"ay is needed. ome operons are repressed"hen the

metabolic path"ay is no longer needed.


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*he lacoperoncontains genes for these of lactose as an energy sorce.

#eglatory regions of the operon inclde

the CAP binding site! promoter! and theoperator.

*he coding region contains genes for 2

en0ymes/ -galactosidase permease and

transacetylase


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*he lacoperon is negati%ely reglated by

a repressor protein/

' lacrepressor binds to the operator to

block transcription

' in the presence of lactose! an inducer

molecle binds to the repressor protein

' repressor can no longer bind to operator

' transcription proceeds


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3n the presence of both glcose and lactose!

bacterial cells prefer to se glcose.

Glcose pre%ents indction of the lacoperon.

' binding of CAP ! cA"P complexto the

CA$ binding site is re&ired for indction of

the lacoperon

' high glcose le%els case lo" cA+$ le%els

' high glcoselo" cA+$no indction


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*he trpoperonencodes genes for the

biosynthesis of tryptophan.

*he operon is not expressed "hen the cell

contains sfficient amonts of tryptophan.

*he operon is expressed "hen le%els of

tryptophan are lo".


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*he trpoperon is negati%ely reglated bythe trprepressor protein

' trprepressor binds to the operator to

block transcription' binding of repressor to the operator

re&ires a corepressor"hich is

tryptophan' lo" le%els of tryptophan pre%ent the

repressor from binding to the operator


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Ekaryotic #eglation

Controlling the expression of ekaryoticgenes re&ires transcription factors.

' general transcription factorsare

re&ired for transcription initiation re&ired for proper binding of #NA

polymerase to the DNA

' specific transcription factorsincreasetranscription in certain cells or inresponse to signals


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Ekaryotic *ranscription

General transcription factors bind to the

promoterregion of the gene.

#NA polymerase 33 then binds to the

promoter to begin transcription at the start

site #$%&.

'nhancersare DNA se&ences to "hich

specific transcription factors 4activators5

bind to increase the rate of transcription.


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Ekaryotic *ranscription

Coactivatorsand mediatorsare also

re&ired for the fnction of transcription

factors.

' coacti%ators and mediators bind to

transcription factors and bind to other

parts of the transcription apparats


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Ekaryotic Chromosome trctre

Ekaryotic DNA is packaged into

chromatin.

Chromatin strctre is directly related to

the control of gene expression.

Chromatin strctre begins "ith the

organi0ation of the DNA into ncleosomes.

Ncleosomes may block #NA polymerase

33 from gaining access to promoters.


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Ekaryotic Chromosome trctre

"ethylation4the addition of 'C)25 of DNA

or histone proteins is associated "ith the

control of gene expression.

Clsters of methylated cytosine ncleotides

bind to a protein that pre%ents acti%ators

from binding to DNA.

+ethylated histone proteins are associated

"ith inacti%e regions of chromatin.


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$osttranscriptional #eglation

Control of gene expression sally in%ol%es

the control of transcription initiation.

t gene expression can be controlled after

transcription! "ith mechanisms sch as/

' #NA interference

'alternati%e splicing

' #NA editing

' m#NA degradation


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RNA interferencein%ol%es the se of

small #NA molecles

*he en0yme Dicerchops doble stranded

#NA into small pieces of #NA

' micro-RNAsbind to complementary

#NA to pre%ent translation

' small interfering RNAsdegrade

particlar m#NAs before translation


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3ntrons are spliced ot of pre(m#NAs to

prodce the matre m#NA that is

translated.

Alternative splicingrecogni0es different

splice sites in different tisse types.

*he matre m#NAs in each tisse possess

different exons! reslting in different

polypeptide prodcts from the same gene.


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RNA editingcreates matre m#NA that

are not trly encoded by the genome.

-or example '

' apolipoprotein exists in 7 isoforms

' one isoform is prodced by editing the

m#NA to create a stop codon' this #NA editing is tisse(specific


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+atre m#NA molecles ha%e %arios

half(li%es depending on the gene and the

location 4tisse5 of expression.

*he amont of polypeptide prodced from

a particlar gene can be inflenced by the

half(life of the m#NA molecles.


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$rotein Degradation

$roteins are prodced and degraded

continally in the cell.

$roteins to be degraded are tagged "ith

ubi(uitin.

Degradation of proteins marked "ith

bi&itin occrs at the proteasome.


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