Chapter 18: Regulation of Gene Expression

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2.e.1 – Timing and coordination of specific events are
necessary for the normal development of an
organism, and these events are regulated by a
variety of mechanisms (18.2-18.4).
 3.b.1 – Gene regulation results in differential gene
expression, leading to cell specialization (18.1-18.3).
 3.b.2 – A variety of intercellular and intracellular
signal transmissions mediate gene expression (18.118.4).
 4.a.3 – Interactions between external stimuli and
regulated gene expression result in specialization of
cells, tissues, and organs (18.4).

 Some
bacteria can regulate their gene
expression based on their surroundings
• E. coli needs tryptophan to survive; if it isn’t
getting trp from its environment (such as the
human colon), then it makes its own
• When the host is ingesting enough trp for the E.
coli, the bacteria inhibits enzyme activity
thereby shutting down the synthesis of trp and
conserving energy.
 Fig. 18.2, page
352
 An operon includes the operator (which
controls the access of RNA polymerase to
the genes), the promoter (a site where
RNA polymerase can bind to DNA and
begin transcription), and all the genes
they control
 Using
trp synthesis as an example:
• The trp operon is turned on meaning that RNA
polymerase can bind to the promoter and
transcribe the genes of the operon
• The trp repressor switches the operon off, and
the repressor binds to the operator blocking
attachment of RNA polymerase to the promoter
preventing gene transcription
• Fig. 18.3, page 353
3
billion base
pairs
 ~30,000 genes
 Total of almost 3
FEET of DNA in
each and every
cell in our bodies
 With
so much DNA in a cell, how is it
organized or packaged?
 How is the expression of the DNA
controlled?
1.
2.
3.
4.
Nucleosomes
Chromatin Fibers
Looped Domains
Chromosomes
Focus on #1 & #4
 "Beads
on a String”
 DNA wound on a protein core
 Packaging for DNA
 Controls transcription
 Two
molecules of four types of Histone
proteins
 H1- 5th type of Histone protein attaches
the DNA to the outside of the core
 Large
units of DNA/chromatin/proteins
 Appear only during cell division (after
Interphase)
 Similar to "Chapters" in the Book of
Life
1. Heterochromatin - highly condensed
chromatin; areas that are not
transcribed
2. Euchromatin - less condensed
chromatin; areas of active
transcription
1. Repetitive Sequences
2. Satellite DNA
3. Interspersed Repetitive DNA
4. Multigene Families
 Give
regions of the DNA different
densities
 Linked to some genetic disorders.
• Ex. - Fragile X Syndrome
• Huntington’s disease
A
collection of identical or very similar
genes
 From a common ancestral gene.
 May be clustered or dispersed in the
genome
 Identical
genes for the same protein
• Ex: Ribosomal Protein and rRNA
 Result
- Many copies of ribosomes
possible
 Most common gene in DNA
 Related
clusters of genes that are nearly
identical in their base sequences.
 Ex: Globin Genes
 Gene
with sequences very similar to
real genes, but lack promoter sites
 Are not transcribed into proteins
 Possible proof of transpositions?
 Changes
in the ways a gene can be
expressed
 Seen only in somatic cells
 Have major effects on gene expression
within particular cells and tissues
1. Gene Amplification
2. Selective Gene Loss
3. Genomic Rearrangements
 The
selective replication of certain genes
 Ex: rRNA genes in eggs
 Result - many copies of rRNA for making
ribosomes
 Loss
of genes or chromosomes in some
tissues during development
 Result - DNA (genes) lost and not
expressed
 Shuffling
of DNA areas (not from meiosis)
 Ex: Transposons retrotransposons
antibody genes
• Examples of Transposons: flower petals
 Complicated
Process
 Many levels of control are possible
 Hint - students should understand several
mechanisms of control (see slides to
follow)
1. Nucleus - those inside the nuclear
membrane
2. Cytoplasm - those that occur in the
cytoplasm
1. Extra-Cellular Signals (Chapter 11 –
Cell communication)
2. Chromatin Modifications
3. Transcriptional Control
4. Posttranscriptional Control
 DNA
Methylation
 Histone Acetylation
 Gene rearrangements
 Gene amplification
 Addition
of methyl groups (-CH3) to DNA
bases
 Result - long-term shut-down of DNA
transcription
 Ex: Barr bodies
 Attachment
of acetyl groups (-COCH3) to
AAs in histones
 Result - DNA held less tightly to the
nucleosomes, more accessible for
transcription
 Ex: Enhancers
• Areas of DNA that increase transcription.
 Ex: DNA-Binding Domains
• Proteins that bind to DNA and regulate
transcription
 Ex: regulatory
RNA.
• Small RNA molecules that are not translated
• Usually interact with DNA
 Result
- genes are more (or less)
available for transcription.
1. RNA Processing
•
Ex - introns and exons
2. RNA Transport
•
moving the mRNA into the cytoplasm
3. RNA Degradation
•
breaking down old mRNA
1. Translation
2. Polypeptide Changes
 Regulated
by the availability of initiation
factors
 Availability of tRNAs, AAs and other
protein synthesis factors
• (Review Chapter 17)
 Changes
to the protein structure after
translation
 Ex: Cleavage
• Modifications
• Activation
• Transport
• Degradation
 Cancer
- loss of the genetic control of cell
division
 Balance between growth-stimulating
pathway (accelerator) and growthinhibiting pathway (brakes)
 Normal
genes for cell growth and cell
division factors
 Genetic changes may turn them into
oncogenes (cancer genes)
 Ex: Gene Amplification, Translocations,
Transpositions, Point Mutations
 Genes
that inhibit cell division
• Ex - p53, p21
 RAS
- a G protein
 When mutated, causes an increase in cell
division by over-stimulating protein
kinases
 Several mutations known
 p53
- involved with several DNA repair
genes and “checking” genes.
 When damaged (e.g. cigarette smoke),
can’t inhibit cell division or cause
damaged cells to apoptose.
 Agents
that cause cancer
• Ex: radiation, chemicals
 Most
work by altering the DNA, or
interfering with control or repair
mechanisms
 See Chapter 17 for more on this!
 Cancer
is the result of several control
mechanisms breaking down
• Ex: Colorectal Cancer requires 4 to 5 mutations
before cancer starts
 Recognize
the operon model for gene
regulation in prokaryotes.
 Identify different mechanisms of eukaryotic
gene expression control.
 Recognize the roles of RNA in controlling
gene expression.
 Recognize examples of differential gene
expression in multicellular organisms.
 Recognize that cancer is caused by changes
in gene regulation.
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