GENE REGULATION
CH18
I. Overview of gene regulation
 Process by which gene expression can be
controlled
 Both prokaryotes and eukaryotes regulate
gene expression in response to
environmental conditions
 Cells only make those proteins that they
need to function, often only making those
proteins at specific times
 In multicelled eukaryotes regulates
development and is responsible for
creating the different cell types
II. Gene regulation in Prokaryotes
A. General characteristics of prokaryotic
gene regulation
 Controlled at the operon
 Components of an operon:
o Regulatory sequences: bind
activators or repressors to turn on
or turn off transcription
o Promoter sequence: binds RNA
polymerase to start transcription
o Coding region: contains the genes
that code for several enzymes for
that metabolic pathway
o In operons, all of the genes for a
metabolic pathway are under the
control of a single on/off switch
 Some operons are repressible operons:
they are usually on and repressor turns
them off (trp operon)
 Some operons are inducible operons: they
are off and inducer turns them on (lac
operon)
 Inducible operons are part of catabolic
pathways while repressible operons are
part of anabolic pathways
B. The lac operon (an inducible operon)
 Involved in the breakdown of lactose for
energy when no glucose is around
 In order for the lac operon to be on:
o Cap protein must bind to activator site
Glucose prevents CAP from binding
o Repressor must be off of the operator
Lactose prevents repressor from binding
http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapt
er12/animation_quiz_4.html
C. Trp operon (a repressible operon)
 Involved in the production of
tryptophan, an amino acid
 Trp operon is on UNLESS there is
excess tryptophan
http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::53
5::535::/sites/dl/free/0072437316/120080/bio2
6.swf::The+Tryptophan+Repressor
III. Eukaryotic gene regulation
 Multicelled eukaryotes are more complex
than prokaryotes so gene regulation
occurs at many levels
 Gene regulation is designed to:
o Maintain homeostasis
o promote cell specialization thru
differential gene expression
A. Regulation of Chromatin structure
 Heterochromatin is tightly packed thus
genes can’t be transcribed
o Acetylation of histones loosens the
heterochromatin allowing it to be
transcribed
o Methylation condenses the DNA
preventing it from being transcribed
which may play role in gene
inactivation during differentiation
Sometimes these chemical modifications of
DNA can be passed on to offspring. This is
called epigenetics
http://learn.genetics.utah.edu/content/epigen
etics/
B. Transcriptional control in Eukaryotes
1. Structure of a typical eukaryotic gene
 Upstream control elements: regulate
transcription initiation by binding
transcription factors
 Promoter: starts transcription
 Coding sequence: in between promoter
and termination sequence
2. role of transcription factors:
 general transcription factors allow
transcription to occur
 activators are transcription factors
that bind to enhancers upstream and
induce transcription
 repressors are transcription factors
than bind to silencers upstream and
inhibit transcription
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapt
er18/animations.html#
 these transcriptional activator and
repressor proteins are activated in
response to environmental cues
o signal molecules bind to receptors…
 cell surface receptors induce
intracellular signal cascade
 cytoplasmic receptor binding
BECOMES the transcription factor
(cell-cell interactions)
http://www.dnatube.com/video/1536/GeneExpression-Animation
C. Post-transcriptional control
 Allows cell to fine tune gene
expression quickly in response to
environmental changes
1. Alternate gene splicing
 Production of different mRNAs from
the same primary transcript
depending on which exons are spliced
together
Example of this?
2. Rate of mRNA degradation
 There are sequences in 3’end of
mRNA that regulate its lifespan
 The quicker the mRNA is degraded,
the less protein made
3. Initiation of translation
 Regulatory molecules can bind to
mRNA that block initiation of
translation
4. Protein processing and degradation
 If a protein is degraded it can’t be
used
5. RNA interference
 Parts of the genome don’t code for
proteins but produce other types of
RNA
 RNA interference is the inhibition
of gene expression by these RNAs
 Small interfering RNAs (siRNA)
binds to mRNA to induce its
degradation
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapt
er18/animations.html#
http://www.youtube.com/watch?v=3S3ZOmleAj0&list=PLFCE4D99C4124A27A&index=40
IV. Differential gene expression and
development in multicelled eukaryotes
 Fertilized egg divides by mitosis to
produce all cells in multicelled eukaryotes
o Cell division produces identical cells
o Cell differentiation produces
specialized cells thru differential gene
expression
o Morphogenesis results in shaping of
organism
 All three events are based on processes
that occur at the cellular level
 Since transcriptional activators stimulate
transcription, then different cells must
have different sets of transcriptional
activators
Different cells express different sets of
genes
What “tells” a cell which genes to express?
A. Cytoplasmic Determinants and
Induction
1. Cytoplasmic Determinants
 proteins, mRNAs, and organelles
aren’t distributed evenly in a fertilized
egg cell
 many of these proteins and mRNAs
are cytoplasmic determinants that
influence the fate of the cells
 when cell divides, determinants are not
equally distributed
 therefore, nuclei in each cell are
exposed to different determinants. This
helps direct what genes are expressed
during cell differentiation
2. Induction
 As the number of cells increases,
different embryonic cells secrete signal
molecules that affect gene expression in
neighboring cells thru the cell signaling
pathway
 This results in changes in gene
expression
Induction and cytoplasmic determinants
lead to formation of 3 germ cell layers
and ultimately all of the specialized cells
in organs and tissues
 Once induction occurs and certain cells
start expressing different genes, those
cells are determined to become a specific
cell type
 The expression of these specific genes
leads to expression of other genes
resulting in cell differentiation
IV. Gene regulation and Cancer
A. Cell Cycle control
 Control of cell cycle is like
accelerator and break
 When new cells are needed,
accelerator is used
 When new cells not needed brake is
used
B. Proto-oncogenes
 Are normal proteins that stimulate
progression thru the cell cycle
 Many are intracellular cell signaling
molecules involved in activating
transcription
 Mutations cause proto-oncogenes to
become oncogenes
 Results in overstimulation of cell
division
 Ex: Ras proto-oncogene
o Normal ras is activated by binding of
growth factor to its receptor
o This activated ras activates a series of
protein kinases that activate a
transcription factor which induces
transcription of cell cycle stimulatory
protein
o Mutated ras does not need growth
factor activtion
C. Tumor Suppressor genes
 Normal tumor suppressor genes inhibit
cell division
o Some repair DNA
o Some involved in anchorage
dependence
o Some are part of cell signaling
pathway that inhibit cell division
 Ex: p53
o DNA damage activates p53 which
induces transcription of a protein that
inhibits cell cycle
o Mutation in p53 fails to induce
transcription of this protein