GENE REGULATION
ch 18
CH18
Bicoid is a protein that is involved in determining
the formation of the head and thorax of
Drosophila.
I. Overview of gene regulation
• Both prokaryotes and eukaryotes regulate gene
expression in response to environmental
conditions
• They only make those proteins that they need
to function, often only making those proteins at
specific times
• This was favored by natural selection. Since all
organisms do this, it evolved early
• In multicelled eukaryotes this also regulates
development and is responsible for creating the
different cell types
II. Gene regulation in Prokaryotes
A. General characteristics of prokaryotic gene
regulation: the operon
• Operon: cluster of functionally related gees
under the control of a single on/off switch:
the operator
• An operon contains the promotor, the
operator, and all the genes under their
control
• The operator binds repressor proteins that
stop transcription by preventing RNA
polymerase from binding to the promoter
• 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
http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapter12/animation_quiz_4.ht
ml
C. Trp operon (a repressible operon)
http://highered.mcgr
awhill.com/olcweb/cgi/p
luginpop.cgi?it=swf::5
35::535::/sites/dl/fre
e/0072437316/12008
0/bio26.swf::The+Try
ptophan+Repressor
Involved in the production of tryptophan, an amino
acid
Trp operon is on UNLESS there is excess tryptophan
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
– Acetylation of histones loosens the
heterochromatin allowing it to be transcribed
– 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/epigenetics/
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/ch
apter18/animations.html#
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
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
https://www.youtube.com/watch?v=cKOGB1_ELE
• 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) bind to
mRNA to induce its
degradation
IV. Differential gene expression and
development in multicelled
eukaryotes
• Fertilized egg divides by mitosis to produce
all cells in multicelled eukaryotes
– Cell division produces identical cells
– Cell differentiation produces specialized cells
thru differential gene expression
– 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
– Normal ras is activated by binding of growth
factor to its receptor
– This activated ras activates a series of protein
kinases that activate a transcription factor which
induces transcription of cell cycle stimulatory
protein
– Mutated ras does not need growth factor
activation
C. Tumor Suppressor genes
• Normal tumor suppressor genes inhibit cell
division
– Some repair DNA
– Some involved in anchorage dependence
– Some are part of cell signaling pathway that
inhibit cell division
Ex: p53
• DNA damage activates p53 which induces
transcription of a protein that inhibits cell cycle
• Mutation in p53 fails to induce transcription of
this protein