AP Biology, Chapter 18

Regulation of Gene Expression

Conducting the Genetic Orchestra
18.1 Bacteria often respond to environmental change by regulating transcription
Intro
1. Briefly describe two main strategies that cells use to control metabolism.
Regulate enzyme activity
End product of the pathway feedback to stop its production
Binds to 1st enzyme in the pathway; non-competitive or allosteric
Regulate gene expression
Turn genes on and off by controlling the initiation of transcription
Takes longer
Operons: The Basic Concept
2. Explain the adaptive advantage of genes grouped into an operon.
Operon = operator, promoter, and the genes they control
Puts functionally related genes under the control of a single on-off switch
Repressible and Inducible Operons: Two Types of negative Gene Regulation
3. Using the trp operon as an example, explain the concept of an operon and the
function of the operator, repressor, and co-repressor.
Separate repressor gene is expressed constitutively
Corepressor = tryptophan
Repressor + tryptophan binds to operator and blocks transcription
When tryptophan is low, repressor alone releases from operator
4. Distinguish between structural and regulatory genes.
Structural genes code of enzymes in a biosynthetic pathway
Regulatory genes code for proteins that turn operons on or off
5. Describe how the lac operon functions and explain the role of the inducer,
allolactose.
Separate repressor gene is expressed constitutively
Repressor alone binds to operator, blocks transcription
Inducer allolactose binds to repressor and it releases from the operator
RNA polymerase can the transcribe the genes required for lactose digestion
6. Explain how repressible and inducible enzymes differ and how those differences
reflect differences in the pathways they control.
Respressible
Small molecule binds respressor and turns off the operon
Useful for anabolic pathways; enough product turns off pathway
Inducible
Small molecule binds repressor and turns on the operon
Useful for catabolic pathways; presence turns on genes to digest
Positive Gene Regulation
7. Distinguish between positive and negative control and give examples of each from
the lac operon.
Negative
Operon switched off by active repressor
Lac repressor without allolactose binds to operator, blocks
transcription
Positive
Operon switched on by active regulatory protein
CRP protein + cAMP binds to DNA, helps RNA polymerase bind to
promoter
= an activator
8. Explain how cyclic AMP and the cyclic AMP receptor protein are affected by glucose

concentration.
Glucose plentiful
cAMP is not made in the cytoplasm
CRP doesn't bind to DNA, RNA polymerase doesn't bind as much
Glucose low
cAMP made
cAMP + CRP bind and increase transcription
18.2 Eukaryotic gene expression is regulated at many stages
Intro
Differential Gene Expression
9. Define differentiation and describe at what level gene expression is generally
controlled.
Differentiation = cellular change in form and function
Control
At transcriptional level
Involves DNA-binding proteins
Coordinated by external signals
Regulation of Chromatin Structure
Intro
Histone Modifications
10. Explain how histone modifications affect chromatin structure and the
regulation of transcription.
Histone acetylation
Loosens nucleosome associations, promotes transcription
Acetyltransferases may be associated with transcription factors
Removal causes nucleosomes to bind
Methylation condenses chromatin
Phosphorylation loosens
Combination and order of modification may be important
DNA Methylation
11. Explain how DNA methylation affects the regulation of transcription.
Methyl groups may be added/removed especially to C
Inactive DNA is often highly methylated; demethylation activates
Methyl inactivation may be passed on during DNA synthesis
Explains genomic imprinting
Epigenetic Inheritance
Regulation of Transcription Initiation
Intro
Organization of a Typical Eukaryotic Gene
12. Define control elements and explain how they influence transcription.
Noncoding sequences where transcription factors bind
May be close (proximal) or far away (distal)
The Roles of Transcription Factors
Intro
13. Describe an example of a general transcription factors.
General are required to transcribe all protein-coding genes
Ex: protein that binds the TATA box
Enhancers and Specific Transcription Factors
14. Describe the activity of enhancers.
Distant (distal) clusters of control elements where proteins bind
DNA folds, bound transcription factors contact RNA polymerase
DNA folding may require specific proteins
15. Describe the two basic structural domains of transcription factors.

Sequence-specific DNA binding domain

Protein-binding domain(s) interact with other transcription
factors, RNA polymerase
16. Contrast the activities of transcription activators and repressors.
Activators are proteins that bind to enhancers
Repressors bind to silencers sequences, block transcription
Combinatorial Control of Gene Activation
17. How varied are control elements and what does that indicate about
how they affect gene expression?
Control elements dont vary much
Each enhancer has about 10
Combination of proteins bound determines time and place of
expression
Coordinately Controlled Genes in Eukaryotes
Nuclear Architecture and Gene Expression
18. How may nuclear architecture affect gene expression?
Chromosomes are mainly segregated
Active chromatin loops may associate in transcription factories
Mechanisms of Post-Transcriptional Regulation
Intro
RNA Processing
19. Describe the process of alternative splicing.
Different mRNAs are produced from the same pre-mRNA
Controlling regulatory proteins bind to pre-mRNA
mRNA Degradation
20. Describe factors that influence the lifetime of mRNA in the cytoplasm.
Compare the longevity of mRNA in prokaryotes and eukaryotes.
Breakdown
Shortening of the poly(A) tail
Removal of the 5' cap
Degradation by nuclease
Lifetime
Prokaryote: very short
Eukaryotes: some very long
Initiation of Translation
21. Explain how gene expression may be controlled at the translational and posttranslational level.
Translational level
Initiation can be blocked
Regulatory proteins may bind to the 5' leader
Global controls can block all translation
mRNAs may be stored
Protein Processing and Degradation
Post-translational level
Processing may be required for functionality
Protein must be routed to its functional location
Proteins may be tagged for destruction in proteasomes with
ubiquitin
18.3 Noncoding RNAs play multiple roles in controlling gene expression
Intro
22. How much of the human genome is composed of protein-coding DNA and how much
is transcribed?
1.5% is traditional genes
But, 90% is transcribed

Effects on mRNAs by MicroRNAs and Small Interfering RNAs

23. How do microRNAs and small interfering RNAs regulate gene expression?
Bind to complementary mRNAs
Either block translation or cause degradation
Chromatin Remodeling and Effects on Transcription by ncRNAs
24. Describe examples of chromatin condensation and transcriptional control involving
ncRNAs.
Transcripts from centromeric DNA bind proteins and the centromere
Piwi-associated RNAs condense regions containing transposons
May also bind promoters and block expression
The Evolutionary Significance of SmallncRNAs
18.4 A program of differential gene expression leads to the different cell types in a
multicellular organism
Intro
A Genetic Program for Embryonic Development
25. Describe three processes involved in embryonic development.
Cell division: new cells form by mitosis
Differentiation: cells become specialized in structure and function
Morphogenesis: parts of organisms change shape
Cytoplasmic Determinants and Inductive Signals
26. Describe the two sources of information that instruct a cell to express genes at
the appropriate time.
Cytoplasmic determinants in the egg
mRNAs and proteins are stored in the unfertilized egg
Many are unevenly distributed, giving a pattern to development
Induction by neighboring cells
Signal molecule may bind to a cell-surface receptor
Induction may result from cell-to-cell contact
Sequential Regulation of Gene Expression During cellular Differentiation
27. Describe the molecular basis of determination.
Determination = "irreversible" commitment to cellular fate
Molecular basis
Changes in transcription
tissue-specific mRNAs
tissue-specific proteins
Example: embryonic precursor cell myoblast muscle cell
Precursors become determined when they express myoD
myoD protein is a transcription factor
Turns on other transcription factors for muscle proteins
Pattern Formation: Setting Up the Body Plan
Intro
The Life Cycle of Drosophila
Genetic Analysis of Early Development: Scientific Inquiry
Intro
28. Describe how Drosophila were used to explain the basic aspects of
pattern formation.
Axis Establishment
Intro
Maternal effect genes (egg-polarity genes) encode the
cytoplasmic determinants
Unequally packed into developing egg
Example bicoid
Bicoid: A Morphogen Determining Head Structures
29. Describe how the normal bicoid gene determines the head-

tail axis in Drosophila.

Homozygous mutant bicoid mothers have embryos with
two tails
Normal bicoid mRNA and protein are found in the
anterior
Injection of normal bicoid mRNA causes anterior
structures to form wherever it is injected
18.5 Cancer results from genetic changes that affect cell cycle control
Intro
Types of Genes Associated with Cancer
Intro
30. Distinguish between proto-oncogenes and oncogenes. Describe three genetic
changes that can convert proto-oncogenes to oncogenes.
Distinction
Oncogenes: cancer causing genes discovered in retroviruses
Homologous normal genes are proto-oncogenes
Proto-oncogene oncogene
Transposition to another regulatory context
Amplification (really duplication)
Point mutation in structural sequence
Tumor-Suppressor Genes
31. Explain how mutations in tumor-suppressor genes can contribute to cancer.
Tumor-suppressor genes make proteins that inhibit cell division
Mutation might eliminate inhibitory activity
Loss of DNA-repair ability
Loss of ability to adhere
Loss of cell cycle control
Interference with Normal cell-Signaling Pathways
32. Explain how excessive cell division can result from mutations in the ras oncogenes.
Normal function of Ras proto-oncogene
Growth factor binds to tyrosine-kinase linked receptor
Activates G protein, a G protein
Activates a series of protein kinases
Causes expression of cell cycle stimulating protein
Mutation in ras
May not need G protein stimulation; activates kinases on its own
Ras may be hyperactive or more long-lasting
33. Explain why a mutation knocking out the p53 gene can lead to excessive cell growth
and cancer. Describe three ways that p53 prevents a cell from passing on mutations
caused by DNA damage.
Normal function of p53 proto-oncogene
Growth-inhibiting factor binds to receptor
Activates G protein
Activates a series of kinases
Activates p53, an activating transcription factor
Turns on a gene making an inhibitory protein
Mutation in p53
Cannot activate gene expression
Inhibitory protein not expressed
Other protective functions of p53
Activates p21; slows cell cycle after DNA damage, allows time for
repair
Turns on DNA repair genes
Triggers apoptosis in cells with irreparable damage

The Multistep Model of Cancer Development

34. Describe the set of genetic factors typically associated with the development of
cancer.
Activation of one (dominant) oncogene
Inactivation of both alleles of (recessive) tumor-suppressor genes
Activation of telomerase
Inherited Predisposition and Other Factors Contributing to Cancer
35. Describe two common inherited cancer alleles.
APC is mutated in 60% of colorectal cancers
Tumor-suppressor
Normally involved in cell migration and adhesion
BRCA-1 and -2
Carrying one BRCA-1 allele increases risk of breast cancer 30-fold
Both are tumor-suppressors
Both normally involved in DNA damage repair
36. Explain how viruses can cause cancer. Describe several examples.
Integrate their DNA into host cell chromosomes
Causes mutation
Can deliver or amplify oncogenes