Regulation of Gene Expression

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Regulation of Gene Expression

• CHAPTER 18

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Bacterial Genome Replication
Section 18.1 Bacteria can respond to
environmental change by regulating gene
transcription

• double-stranded, circular DNA located in the
  nucleoid region
• many bacteria also have plasmids smaller
  circles of DNA with a few genes
• reproduce by binary fission
• therefore, most bacteria in a colony are
  genetically identical
• genetic diversity can arise as a result of
  mutation especially when reproductive rates are
  high (short generation spans)

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Metabolic Control in Bacteria

• adjust the activity of enzymes already present
  via chemical cues
• (ex) feedback inhibition
• adjust the amount of enzyme being made by
  regulating gene expression
• basic mechanism is described in the operon model

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Operons
operator
gene A
gene B
gene C
gene D
promoter

• made up of an operator, promoter, a set of
  functionally related genes
• operator segment of DNA that acts like an
  on/off switch for transcription positioned w/in
  promoter or between promoter genes
• promoter site where RNA polymerase binds to DNA
  begins transcription
• set of genes transcription unit

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Example trp operon
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lac operon

• repressor protein requires a small molecule
  called an inducer to make the repressor inactive
  (the repressor unblocks the path)

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Section 18.2 Gene expression can be regulated
at any stage
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Regulation at Structural Levels of DNA

• a single linear DNA double helix averages about 4
  cm in length
• DNA associates with proteins that condense it so
  it will fit in the nucleus
• DNA-protein complex chromatin
• chromatin looks like beads on a string when
  unfolded
• beads nucleosomes made up of histones
  (proteins)
• string DNA

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Structural Levels of DNA
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• chromatin fiber (30 nm)
• created by interactions between adjacent
  nucleosomes and the linker DNA
• chromatin fiber (300 nm)
• created when the 30 nm chromatin fiber forms
  loops called looped domains attached to a protein
  scaffold made of nonhistones
• chromosome
• forms when the 300 nm chromatin fiber folds on
  itself

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Regulation of Chromatin Structure

• compactness of chromatin helps regulate gene
  expression
• heterochromatin highly compact so it is
  inaccessible to transcription enzymes
• euchromatin less compact allowing transcription
  enzymes access to DNA
• chemical modifications that can alter chromatin
  compactness
• histone acetylation (-COCH3) neutralizes the
  histones so they no longer bind to neighboring
  nucleosomes causing chromatin to have a looser
  structure

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DNA Methylation

• addition of methyl groups to DNA bases (usually
  cytosine) inactivates DNA
• methylation patterns can be passed on
• after DNA replication, methylation enzymes
  correctly methylate the daughter strand
• accounts for genomic imprinting in mammals
  expression of either the maternal or paternal
  allele of certain genes during development
• (NOTE inheritance of chromatin modifications
  that do not involve a change in the DNA sequence
  is called epigenetic inheritance)

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Regulation at Transcription

• Regulation at level of transcription results in
  differential gene expression
• Most common way that gene expression is regulated

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Regulation of Transcription Initiation

• general transcription factors proteins that
  form a transcription initiation complex on the
  promoter sequence (ex TATA box) allowing RNA
  polymerase to begin transcription
• control elements segments of noncoding DNA that
  help regulate transcription by binding certain
  proteins
• proximal control elements
• distal control elements (enhancers) - interact
  with specific transcription factors
• activators stimulate transcription by binding to
  enhancers
• repressors - inhibit transcription by binding
  directly to enhancers or by blocking activator
  binding to enhancers or other transcription
  machinery

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1. activators bind to enhancer with 3-binding sites
2. a DNA-bending protein brings the bound activators
   closer to the promoter
3. activators bind to general transcription factors
   mediator proteins, helping them to form a
   functional transcription initiation complex

• activators can also promote histone acetylation
  repressors can promote histone deacetylation

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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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Regulation of RNA splicing

• In alternative RNA splicing, different mRNA
  molecules are produced from the same primary
  transcript, depending on which RNA segments are
  treated as exons and which as introns

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Fig. 18-11
Exons
DNA
Troponin T gene
Primary RNA transcript
RNA splicing
or
mRNA
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Regulation of Protein Lifespan

• After translation, various types of protein
  processing, including cleavage and the addition
  of chemical groups, are subject to control
• Proteasomes are giant protein complexes that bind
  protein molecules and degrade them

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Fig. 18-12
Proteasome and ubiquitin to be recycled
Ubiquitin
Proteasome
Ubiquitinated protein
Protein fragments (peptides)
Protein to be degraded
Protein entering a proteasome
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Gene Regulation
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protein processing degradation
1 2. transcription - DNA packing -
transcription factors 3 4. post-transcription
- mRNA processing - splicing - 5 cap
poly-A tail - breakdown by siRNA 5.
translation - block start of translation 6
7. post-translation - protein processing -
protein degradation
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4
initiation of translation
mRNAprocessing
2
1
initiation of transcription
mRNA protection
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mRNA splicing
3
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Section 18.4 A program of differential gene
expression leads to different cell types in a
multicellular organism
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Embryonic Development

• Zygote transforms as a result of 3 processes
• cell division
• Number of cells increases through mitosis
• cell differentiation
• process by which cells become specialized in
  structure function
• morphogenesis
• Organization of cells into tissues and organs

Cell differentiation arises primarily from
differences in gene expression not from
differences in the cells genomes -
Differentiation and morphogenesis are controlled
by both cytoplasmic determinants and cell to cell
signals
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Cytoplasmic Determinants

• maternal substances in the egg that influence the
  course of early development
• distributed unevenly to new cells produced by
  mitotic division of the zygote
• the set of cytoplasmic determinants a cell
  receives helps regulate gene expression

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Cell to Cell Signals

• communication between cells can induce
  differentiation
• Process is called induction

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Determination

• the events that lead to the observable
  differentiation of a cell
• at the end of this process, an embryonic cell is
  irreversibly committed to its final fate
  (determined)
• marked by the expression of genes for tissue
  specific proteins, which act as transcription
  factors for genes that help define cell type

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Pattern Formation

• development of a spatial organization in which
  the tissues and organs of an organism are all in
  their characteristic places
• begins in early embryo when the major axes of the
  organism are established
• molecular cues (positional information) that
  control pattern formation are provided by
  cytoplasmic determinants inductive signals

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Identity of Body Parts

• controlled by homeotic genes
• turned on by segment-polarity gene products
• specify the types of appendages and other
  structures that each segment will form
• (why are homeotic genes found in clusters?)

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Example of a homeotic gene PAX-6
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Section 18.5 Cancer results from genetic
changes that affect cell cycle control

• The gene regulation systems that go wrong during
  cancer are the very same systems involved in
  embryonic development
• Cancer can be caused by mutations to genes that
  regulate cell growth and division
• Tumor viruses can cause cancer in animals
  including humans

• Oncogenes are cancer-causing genes
• Proto-oncogenes are the corresponding normal
  cellular genes that are responsible for normal
  cell growth and division