Post on 01-Apr-2015
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”