Ch. 18 Regulation of Gene Expression

Objectives:

LO 3.18 The student is able to describe the connection between the regulation of gene expression and observed differences between different kinds of organisms.LO 3.19 The student is able to describe the connection between the regulation of gene expression and observed differences between individuals in a population.LO 3.20 The student is able to explain how the regulation of gene expression is essential for the processes and structures that support efficient cell function.LO 3.21 The student can use representations to describe how gene regulation influences cell products and function.LO 3.22 The student is able to explain how signal pathways mediate gene expression, including how this process can affect protein production..LO 3.23 The student can use representations to describe mechanisms of the regulation of gene expression.

18.1 Bacteria Often Respond to Environmental Change by Regulating Transcription

Conserve resources 1 of 2 ways:• Feedback inhibition (discussed in Ch. 8)• Regulation of gene expression (discussed here)

Precursor

Feedbackinhibition

Enzyme 1

Enzyme 2

Enzyme 3

Tryptophan

(a) (b)Regulation of enzymeactivity

Regulation of enzymeproduction

Regulationof geneexpression

trpE gene

trpD gene

trpC gene

trpB gene

trpA gene

Operons: The Basic Concept and Negative Gene Regulation

Operons:• Operator (“on/off switch”), promoter, and genes.

– Repressible (anabolic) operons: Always “on” until repressor is bound. (inhibited)

• Corepressor is like feedback inhibition (product works with repressor)• Ex: tryptophan producing genes

Promoter

DNA

Regulatory genemRNA

trpR

5

3

Protein Inactive repressor

RNApolymerase

Promoter

trp operon

Genes of operon

Operator

mRNA 5Start codon Stop codon

trpE trpD trpC trpB trpA

E D C B A

Polypeptide subunits that make upenzymes for tryptophan synthesis

(a) Tryptophan absent, repressor inactive, operon on

(b) Tryptophan present, repressor active, operon off

DNA

mRNA

Protein

Tryptophan (corepressor)

Activerepressor

No RNAmade

• Inducible (catabolic) operons are usually off but can be induced.– Inducer inactivates the repressor– Ex: lac (lactose) operon

(a) Lactose absent, repressor active, operon off

(b) Lactose present, repressor inactive, operon on

Regulatorygene

Promoter

Operator

DNA lacZlacI

lacI

DNA

mRNA5

3

NoRNAmade

RNApolymerase

ActiverepressorProtein

lac operon

lacZ lacY lacADNA

mRNA

5

3

Protein

mRNA 5

Inactiverepressor

RNA polymerase

Allolactose(inducer)

-Galactosidase Permease Transacetylase

Positive Gene Regulation

• Gene is always on but activator stimulates transcription.– Ex: cAMP

Promoter

DNA

CAP-binding site

lacZlacI

OperatorRNApolymerase lesslikely to bind

Inactive lacrepressor

InactiveCAP

(b)Lactose present, glucose present (cAMP level low):little lac mRNA synthesized

Promoter

DNA

CAP-binding site

lacZlacI

RNApolymerasebinds andtranscribes

Operator

cAMPActiveCAP

InactiveCAP

Allolactose

Inactive lacrepressor

(a) Lactose present, glucose scarce (cAMP level high):abundant lac mRNA synthesized

18.2 Eukaryotic Gene Expression is Regulated at Many Stages

• Each cell of multicellular organisms contain all genetic info; only some is expressed (differential gene expression).– Each process has the

potential for regulation.

Signal

NUCLEUSChromatin

Chromatin modification:DNA unpacking involvinghistone acetylation andDNA demethylation

DNA

Gene

Gene availablefor transcription

RNA ExonPrimary transcript

Transcription

Intron

RNA processing

Cap

TailmRNA in nucleus

Transport to cytoplasm

CYTOPLASM

mRNA in cytoplasm

TranslationDegradationof mRNA

Polypeptide

Protein processing, suchas cleavage and chemical modification

Active proteinDegradationof protein

Transport to cellulardestination

Cellular function (suchas enzymatic activity,structural support)

Regulation of Chromatin Structure

• Histone Modifications: acetylation loosens chromatin easier protein access.

• DNA Methylation: addition of methyl group to gene turns it off.

• Epigenetic Inheritance: gene regulation passed on to offspring.

Amino acidsavailablefor chemicalmodification

Histone tails

DNA double helix

Nucleosome(end view)

(a) Histone tails protrude outward from a nucleosome

Unacetylated histones Acetylated histones

(b) Acetylation of histone tails promotes loose chromatinstructure that permits transcription

Regulation of Transcription Initiation

• Control elements/enhancers upstream from a gene can activate or repress transcription factors to regulate gene expression.

• Combination of control elements and their activators.– Like genes use similar control elements and

activators.

Mechanisms of Post-Transcriptional Regulation

• mRNA degradation• Alternative RNA splicing: different

intron/exons spliced together.Exons

DNA

Troponin T gene

PrimaryRNAtranscript

RNA splicing

ormRNA

1

1

1 1

2

2

2 2

3

3

3

4

4

4

5

5

5 5

© 2011 Pearson Education, Inc.

Animation: Blocking TranslationRight-click slide / select “Play”

© 2011 Pearson Education, Inc.

Animation: Protein ProcessingRight-click slide / select “Play”

18.3 Noncoding RNAs Play Multiple Roles in Controlling Gene Expression

• Parts of DNA that make very small RNA (ncRNA) but not proteins; regulate gene expression.– Bind to a complementary sequence of mRNA, blocking translation.– Bind to DNA changing chromatin structure1. microRNAs (miRNA): begins as hairpin2. Small interfering RNAs (siRNA): begins as double strand

(a) Primary miRNA transcript

HairpinmiRNA

miRNA

Hydrogenbond

Dicer

miRNA-proteincomplex

mRNA degraded Translation blocked(b) Generation and function of miRNAs

5 3

18.4 A Program of Differential Gene Expression Leads to the Different Cell Types in a Multicellular Organism

• Embryonic development:division differentiation morphogenesis

Cytoplasmic Determinants• RNA and proteins from

mom’s cell unevenly distributed giving rise to different cells during 1st divisions.

(a) Cytoplasmic determinants in the egg

Unfertilized egg

Sperm

Fertilization

Zygote(fertilized egg)

Mitoticcell division

Two-celledembryo

Nucleus

Molecules of twodifferent cytoplasmicdeterminants

Induction is how embryonic cells effect one another due to cell-surface molecules or growth factors.

Determination due to the expression of genes for tissue-specific proteins.

Pattern Formation puts determined cells in their “proper places” for the resulting organism.

Morphogens (proteins) establish an embryo’s axes

(b) Induction by nearby cells

Early embryo(32 cells)

NUCLEUS

Signaltransductionpathway

Signalreceptor

Signalingmolecule(inducer)

© 2011 Pearson Education, Inc.

Animation: Development of Head-Tail Axis in Fruit FliesRight-click slide / select “Play”