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 Feedback inhibition trpE gene Enzyme 1 trpD gene Regulation of gene expression Enzyme 2 trpC gene



trpB gene



Enzyme 3 trpA gene Tryptophan (a) Regulation of enzyme activity (b) Regulation of enzyme production

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

DNA Promoter Regulatory gene mRNA Protein 5



trpR

3



Inactive trp operon RNA Promoter polymerase Operator Start codon mRNA 5



trpE

Genes of operon

trpD

Stop codon

trpC

repressor (a) Tryptophan absent, repressor inactive, operon on

trpB

E D C B Polypeptide subunits that make up enzymes for tryptophan synthesis

trpA

A DNA No RNA made mRNA Protein Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off Active repressor

•

mRNA

Inducible (catabolic) operons are usually off but can be induced.

– – Inducer inactivates the repressor Ex: lac (lactose) operon

Promoter Regulatory gene

lac I

Operator

lacZ

No RNA made 3



5



RNA polymerase Protein Active repressor (a) Lactose absent, repressor active, operon off lac operon

lac I

DNA

lacZ lacY lacA

mRNA 3



RNA polymerase mRNA 5



5

 

-Galactosidase Protein Allolactose (inducer) Inactive repressor (b) Lactose present, repressor inactive, operon on Permease Transacetylase

Positive Gene Regulation

• Gene is always on but activator stimulates transcription.

– Ex: cAMP

Promoter DNA

lac I

CAP-binding site

lacZ

Operator RNA polymerase less likely to bind Inactive CAP Inactive lac repressor (b)Lactose present, glucose present (cAMP level low): little lac mRNA synthesized Promoter DNA

lac I

CAP-binding site Active CAP

lacZ

RNA polymerase binds and transcribes Operator cAMP Inactive CAP Allolactose Inactive lac repressor (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized

18.2 Eukaryotic Gene Expression is Regulated at Many Stages

Signal

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

– Each process has the potential for regulation.

DNA Cap RNA NUCLEUS Chromatin Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation Gene available for transcription Gene Transcription Exon Primary transcript Intron RNA processing Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Degradation of protein Polypeptide Protein processing, such as cleavage and chemical modification Active protein Transport to cellular destination Cellular function (such as enzymatic activity, structural support)

Regulation

of Chromatin Structure

Histone tails Amino acids available for chemical modification 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 chromatin structure that permits transcription

• • • 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.

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 1 2 3 Troponin T gene 4 5 Primary RNA transcript 1 2 3 4 5 mRNA 1 2 3 5 RNA splicing or 1 2 4 5

© 2011 Pearson Education, Inc.

Animation: Blocking Translation Right click slide / select “Play”

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Animation: Protein Processing Right 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 structure 1.

2.

microRNAs (miRNA): begins as hairpin Small interfering RNAs (siRNA): begins as double strand

Hairpin miRNA Hydrogen bond Dicer 5



3



(a) Primary miRNA transcript miRNA miRNA protein complex mRNA degraded Translation blocked (b) Generation and function of miRNAs

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 1 st divisions.

(a) Cytoplasmic determinants in the egg Unfertilized egg Sperm Fertilization Zygote (fertilized egg) Mitotic cell division Nucleus Molecules of two different cytoplasmic determinants Two-celled embryo

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

(b) Induction by nearby cells Early embryo (32 cells)

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

Signal transduction pathway Signal receptor Signaling molecule (inducer) NUCLEUS

© 2011 Pearson Education, Inc.

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