Regulation of Gene Expression

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Regulation of Gene Expression

• Chapter 18

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Activity

• Watch video and listen.
• After video, complete worksheet.

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REGULATION

• What is Regulation?
• Every cell in your body has the exact same
  genetic code sequence
• Each cell will not use all of its genes
• Cells will only turn on the genes that relate to
  its function!

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Regulation of Gene Expression by Bacteria

• Single-celled organisms

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Bacterial Genomes

• DNA-most is found in the nucleoid region
• Most bacteria have plasmids
• much smaller circles of DNA, each with only a few
  genes

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Regulation of metabolic pathways
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Bacterial control of gene expression

• Operon cluster of related genes with on/off
  switch
• Four Parts
• Promoter where RNA polymerase attaches
• Repressor-blocks polymerase
• Operator on/off, controls access of RNA poly
• Genes code for related enzymes in a pathway

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• Regulatory gene produces repressor protein that
  binds to operator to block RNA poly

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Repressible Operon (ON ? OFF)
Inducible Operon (OFF ? ON)
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trp operon
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http//highered.mheducation.com/sites/0072995246/s
tudent_view0/chapter7/the_trp_operon.html
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lac operon
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https//highered.mheducation.com/sites/9834092339/
student_view0/chapter15/the_lac_operon.html
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Answer the following

• What is the difference between inducible and
  repressible operons?

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Positive Gene Regulation

• Protein or enzyme can enhance the operon function
• Ex. Occurs in the lac operon

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Fig. 18-5
Promoter
Operator
DNA
lacI
lacZ
RNA polymerase binds and transcribes
CAP-binding site
Active CAP
cAMP
Inactive lac repressor
Inactive CAP
Allolactose
(a) Lactose present, glucose scarce (cAMP level
high) abundant lac mRNA synthesized
Promoter
Operator
DNA
lacI
lacZ
CAP-binding site
RNA polymerase less likely to bind
Inactive CAP
Inactive lac repressor
(b) Lactose present, glucose present (cAMP level
low) little lac mRNA synthesized
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Answer the following

• What is the role of cAMP and CAP? When do we see
  these molecules?

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Regulation of Gene Expression in Eukaryotes

• Many stages

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Human Genome

• 3 billion base pairs of DNA
• Only 24,000 genes
• Not all DNA will code for proteins
• Noncoding DNA (Ex. telomeres)

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1) Regulation of Chromatin Structure

• chromatin-DNA and proteins
• histones-proteins
• nucleosome-beads that contain DNA and histones

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Regulation of Chromatin Structure

• More transcription acetyl group (-COCH3) is
  added to histones and loosens chromatin
• Less transcription methyl group (CH3) is added
  and chromatin tightly packed

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Genomic Imprinting

• Example of methylation
• involves autosomes
• one allele is silenced
• inherit only one working copy (could come from
  mom or dad)
• gene is silenced during egg or sperm formation

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Barr Body

• Example of methylation
• One X is turned off in each cell of a female

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2) Regulation of Transcription

• Enhancers-increase transcription by binding to
  activators
• Transcription factors-proteins that help RNA
  poly. to bind
• Very specific to each cell in the body

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Fig. 18-10
Enhancer
Promoter
Albumin gene
Control elements
Crystallin gene
LENS CELL NUCLEUS
LIVER CELL NUCLEUS
Available activators
Available activators
Albumin gene not expressed
Albumin gene expressed
Crystallin gene not expressed
Crystallin gene expressed
(b) Lens cell
(a) Liver cell
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3) Regulation of mRNA

• Alternative RNA splicing-different mRNA can be
  made from one gene
• Pre-mRNA turns into functional mRNA
• Every mRNA has its own lifespan
• mRNA can translate protein for hours or weeks

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4) Regulation of Translation

• microRNAs and small interfering RNAs can either
  degrade the mRNA or block the mRNA from being
  translated
• RNA interference- blocking of gene expression by
  noncoding RNAs (miRNA siRNA)

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5) Regulation of Proteins

• New protein made must be folded
• Some need to be activated by enzymes
• Proteins may not need to remain in the cells
  forever and can be degraded

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Epigenetic Inheritance and the affect of
expression of genes

• changes to the genome that does not directly
  involved DNA bases
• can be reversed
• environment-stress, diet, nutrition, temperature
  can alter expression of genes

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• http//highered.mcgraw-hill.com/olcweb/cgi/pluginp
  op.cgi?itswf535535/sites/dl/free/0072437316
  /120080/bio31.swfControl20of20Gene20Expressio
  n20in20Eukaryotes

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mRNA Alternative Splicing and mRNA processing

• Different mRNA can be produced depending on which
  sections are introns or exons
• Adding the cap and tail

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mRNA Degradation

• mRNA has a life span
• The mRNA life span is determined by sequences in
  the leader and trailer regions (UTR sections)

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Regulation of Translation

• The initiation of translation can be blocked by
  regulatory proteins that bind to sequences or
  structures of the mRNA

• Proteasomes-giant protein complexes that bind
  protein molecules and degrade them

Proteasome and ubiquitin to be recycled
Ubiquitin
Proteasome
Ubiquitinated protein
Protein to be degraded
Protein fragments (peptides)
Protein entering a proteasome
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• Regulation of mRNA
• micro RNAs (miRNAs) and small interfering RNAs
  (siRNAs) can bind to mRNA and degrade it or block
  translation

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Summary of Eukaryotic Gene Expression
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Embryonic Development of Multicellular Organisms

• Section 18.4

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Embryonic DevelopmentZygote ? Organism

1. Cell Division large identical cells through
   mitosis
2. Cell Differentiation cells become specialized in
   structure function
3. Morphogenesis creation of form organisms
   shape

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Determination irreversible series of events that
lead to cell differentiation
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• Cytoplasmic determinants maternal substances in
  egg distributed unevenly in early cells of embryo

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• Induction cells triggered to differentiate from
  neighboring cells
• Cell-Cell Signals molecules produced by one cell
  influences neighboring cells
• Ex. Growth factors

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Pattern formation setting up the body plan
(head, tail, L/R, back, front)
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Morphogens substances that establish an embryos
axes
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Homeotic genes master control genes that control
pattern formation (ex. Hox genes)
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Cancer results from genetic changes that affect
cell cycle control

• Section 18.5

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Control of Cell Cycle

• Proto-oncogene stimulates cell division
• Tumor-suppressor gene inhibits cell division
• Mutations in these genes can lead to cancer

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• Proto-Oncogene

• Oncogene

• Gene that stimulates normal cell growth division

• Mutation in proto-oncogene
• Cancer-causing gene
• Effects
• Increase product of proto-oncogene
• Increase activity of each protein molecule
  produced by gene

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Proto-oncogene ? Oncogene
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Genes involved in cancer

• Ras gene stimulates cell cycle (proto-oncogene)
• Mutations of ras occurs in 30 of cancers
• p53 gene tumor-suppresor gene
• Functions halt cell cycle for DNA repair, turn
  on DNA repair, activate apoptosis (cell death)
• Mutations of p53 in 50 of cancers

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• Cancer results when mutations accumulate (5-7
  changes in DNA)
• Active oncogenes loss of tumor-suppressor genes
• The longer we live, the more likely that cancer
  might develop

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Fig. 19.12
Growth factor
MUTATION
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Hyperactive Ras protein (product
of oncogene) issues signals on its own
Ras
G protein
GTP
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Ras
GTP
Receptor
Protein kinases (phosphorylation cascade)
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NUCLEUS
Transcription factor (activator)
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DNA
Gene expression
Protein that stimulates the cell cycle
(a) Cell cyclestimulating pathway
Protein kinases
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MUTATION
Defective or missing transcription factor,
such as p53, cannot activate transcription
Active form of p53
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UV light
DNA damage in genome
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DNA
Protein that inhibits the cell cycle
(b) Cell cycleinhibiting pathway
EFFECTS OF MUTATIONS
Protein overexpressed
Protein absent
Cell cycle not inhibited
Cell cycle overstimulated
Increased cell division
(c) Effects of mutations
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Summary

• Embryonic development occurs when gene regulation
  proceeds correctly
• Cancer occurs when gene regulation goes awry