Regulation of

Gene Expression

Sumber : © 2017 W. H. Freeman and

Company
 Ways to Regulate Protein
Concentration in a Cell

• Synthesis of primary RNA transcript

• How to process this RNA into mRNA
• Posttranscriptional modifications of mRNA
• Degradation of mRNA
• Protein synthesis
• Posttranslational modification of protein
• Targeting and transport of the protein
• Degradation of the protein
Seven Processes That Affect
the Steady-State
Concentration of a Protein
 Trends in Understanding Gene
Regulation

• Past focus has been on understanding

transcription initiation.
• There is increasing elucidation of
posttranscriptional and translational
regulation.
• Mechanisms can be elaborate and
interdependent, especially in development.
• Regulation relies on precise protein-DNA and
protein-protein contacts.
 The Vocabulary of Gene Regulation

• Housekeeping gene
• under constitutive expression
• constantly expressed in approximately all cells
• Regulated gene
• Levels of the gene product rise and fall with
the needs of the organism.
• Such genes are inducible.
• able to be turned on
• Such genes are also repressible.
• able to be turned of
 RNA Polymerase Binding to
Promoters Is a Major Target
of Regulation
• RNA polymerases bind to promoter
sequences near the starting point of
transcription initiation.

• The RNA pol-promoter interaction greatly

influences the rate of transcription initiation.

• Regulatory proteins (transcription factors)

work to enhance or inhibit this interaction
between RNA pol and the promoter DNA.
 A Consensus Sequence Is Found in Many E.
Coli Promoters

• Most bacterial promoters include the

conserved –10 and –35 regions that interact
with the  factor of RNA polymerase.
• Substitutions in this –10 to –35 region usually
reduce the affinity of RNA Pol for the promoter.
• Some promoters also include the upstream
element that interacts with the  subunit of
RNA polymerase.
 Mechanisms to Regulate
Transcription in Bacteria
• Use of σ factors
• recognize diferent classes of promoters
• allows coordinated expression of diferent sets of genes
• Binding other proteins (transcription factors) to
promoters
• recognize promoters of specific genes
• may bind small signaling molecules
• may undergo posttranslational modifications
• protein’s affinity toward DNA is altered by ligand binding
or posttranslational modifications
• allows expression of specific genes in response to signals
in the environment
 Regulation by Specificity Factors Such as  Subunits of RNA Pol

• Specificity factors alter RNA polymerase’s

affinity for certain promoters.
• Example:  subunit of E. coli RNA Pol
• Most E. coli promoters recognized by 70.
• This subunit can be replaced by one of six
additional specificity factors.
• Heat shock will replace 70 with 32 and direct
RNA Pol to diferent promoters.
 Heat Shock Induces Transcription
of New Products to Protect Cell

• Occurs when bacteria are subject to heat

stress
• RNA Pol replaces 70 with 32
• Causes RNA Pol to bind to diferent set of
promoters
 transcription of new products including
chaperones that keep proteins in correct
conformation, even in heat
 Small-Molecule Effectors Can
Regulate Activators and Repressors

• Repressors reduce RNA Pol-promoter

interactions or block the polymerase.
• bind to operator sequences on DNA
• usually near a promoter in bacteria but further away
in many eukaryotes

• Effectors can bind to repressor and induce

a conformational change.
• change may increase or decrease repressor’s
affinity for the operator and thus may increase
or decrease transcription
 Activators Improve Contacts
Between
RNA Polymerase and the
Promoter
• Binding sites in DNA for activators are called
enhancers.
• In bacteria, enhancers are usually adjacent
to the promoter.
• often adjacent to promoters that are “weak”
(bind RNA polymerase weakly), so the activator
is necessary
• In eukaryotes, enhancers may be very
distant from the promoter.
 Negative Regulation

• Negative regulation involves repressors.

• Example: Repressor binds to DNA and shuts
down transcription
• Alternative: Signal causes repressor to
dissociate from DNA; transcription induced

Despite opposite effects

on transcription, both
are negative regulation
 Positive Regulation

• Positive regulation involves activators.

• Enhance activity of RNA polymerase
• Activator-binding
sites are near
promoters that
weakly bind RNA
Pol or do not bind
at all.
• It may remain
bound until a
molecule signals
dissociation.
• Alternatively, the
activator may only
 DNA Looping Allows Eukaryotic
Enhancers to Be Far from Promoters

• Activators can influence

transcription at
promoters thousands of
bp away.
• How? Via formation of
DNA loops
• Looping can be facilitated
by architectural
regulator proteins.
• Co-activators may
mediate binding by
binding to both activator
and RNA polymerase.
 Many Bacterial Genes Are
Transcribed And Regulated
Together in an Operon
• An operon is a cluster of genes sharing a
promoter and regulatory sequences.
• Genes are transcribed together, so mRNAs are
several genes represented on one mRNA
(polycistronic).
• First example: the lac operon
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