Control of Gene

Expression
drh. Wawid Purwatiningsih, M.Vet
Veterinary Medicine Faculty
Brawijaya University
Summary
Gene Regulation General
Strategy for Controlling Genes
Gene Regulation in Bacteria
Lac operon
Gene Regulation in Eukaryotes
Gene Control

Why Control?
Some genes are on (being transcribed)
almost all the time.
Called housekeeping genes
Examples: ribosome components, enzymes
used in basic metabolic pathways

Many genes are only turned on when they

are needed.
Gene Control

Why Control?

Transcribing genes that are not needed is a

waste of energy and may interfere with
the status of the cell.
Gene Control

Regulation in Eukaryotes

Respond to a Range of Stimuli

Prokaryotes respond to external stimuli (food
detected, metabolizing enzymes turned on)
Eukaryotes also respond to internal stimuli
(some types of cells release hormones, growth
factors, etc., that affect other types of cells)
Gene Control

Regulation in Eukaryotes

Developmentally Regulated
Multicellular organisms progress through
developmental stages
Different genes expressed at different times
during development
Gene Control

Regulation in Eukaryotes
Cell Specialization in Multicellular Organisms
Cell differentiation is a result of differences in
gene expression
Different genes expressed in different cells
Gene Control > Strategy

Gene control is control over amount of

gene product (RNA or protein) in cell
Multiple ways to control the amount of
gene product in a cell
Gene Control > Strategy

Controlling Gene Product Amount

1. Rate of transcription: rate mRNA is produced;
faster produced = more product
2. mRNA degradation: rate mRNA is broken down;
faster broken down = less product
3. mRNA processing: capping, polyadenylation,
splicing; slower processing = less product
4. Translation: rate of translation or number of
ribosomes translating; fast/more = more product
Gene Control > Strategy

Although control probably involves all of

these, the most understood are changes in
the rate of transcription.
Gene Control > Lac Operon

Gene Expression in Bacteria

Regulation of lac operon is a classic example

Bacteria have 3 genes in a row (operon) that

involve breaking down lactose for energy
In order to be efficient, these genes should not
be expressed unless lactose is present.
Gene Control > Lac Operon

Goal:
Transcription low when lactose is absent
Lac I (gene upstream from operon) produces a
repressor which binds to promoter region.

Binding of repressor prevents RNA

polymerase from binding and transcribing
genes
Gene Control > Lac Operon

Goal:
Increase transcription when lactose is present
Allolactose will bind to the repressor,
changing its conformation and causing it to fall
off the promoter site
Promoter site now available for RNA
polymerase to bind; transcription of lac genes
begins
Gene Control > Lac Operon

Lactose vs. Allolactose:

Gene Control > Lac Operon

Goal:
Turn off transcription when lactose is used up
Allolactose binding is an equilibrium event.
As it dissociates, it is metabolized by
-galactosidase
The free repressor is available to bind the
promoter site and stop transcription
Gene Control > Lac Operon

If both glucose and lactose are present, it is

more efficient for the bacteria to utilize
glucose, and not worry about lactose.

A system is in place where the presence of

glucose can prevent the metabolization of
lactose.
Gene Control > Lac Operon

Goal:
Decrease transcription if lactose and glucose
are present.
Glucose inhibits adenylate cyclase, which
produces cAMP.

High glucose = low cAMP

Gene Control > Lac Operon

Goal:
Decrease transcription if lactose and glucose
are present.
cAMP binds catabolite activator protein
(CAP), which is then able to bind the cap site
upstream of the promoter.
CAP binding needed to stimulate binding of
RNA polymerase and transcription.
Gene Control > Lac Operon

Goal:
Decrease transcription if lactose and glucose
are present.
High glucose = low cAMP = low cAMP-CAP
complex = low transcription = lactose not used

Low glucose = High cAMP = high cAMP-CAP

complex = high transcription possible (lactose
used)
Gene Control > Lac Operon

Lesson from lac Operon:

Binding sites upstream of transcription origin.

Proteins binding to these sites can repress or
activate transcription