genetics - 10/04/21
Gene regulation in Bacteria
Summary
Transcriptional regulation
The term gene regulation means that the level of gene expression can differ under particular conditions.
Genes that are unregulated are termed constitutive.
● They are constantly expressed
● Frequently, constitutive genes encode proteins that are frequently crucial for the survival of the cell/organism →
expressed in all cell types
The benefit of regulating genes is that encoded proteins/RNAs will be produced only when required.
Gene regulation is important for cellular processes such as
1. Metabolism
2. Response to environmental stress
3. Cell division
4. Differentiation and development
5. Several other reasons (cell fitness etc.)
Regulation of gene expression:
1. Transcription – Gene → mRNA
2. Translation – mRNA → protein
3. Post translation – Protein → functional protein
It is essential to study this process in prokaryotes because some of them are still an issue for our health. With the knowledge of
the study, we can have more treatments.
The most frequent way to regulate gene expression in bacteria is at the transcription initiation level
● The rate of mRNA production can be increased or decreased
Transcriptional regulation involves the actions of two main types of regulatory proteins
● Repressors → Bind directly or indirectly to DNA and inhibit transcription: negative control
● Activator → Bind directly or indirectly to DNA and increase transcription: positive control
Small effector molecules influence transcription regulation
● Small effector molecules are sometimes called ligands → short peptides (hormones, neurotransmitters, etc.),
metabolites, drugs …
● These bind to regulatory proteins and not to DNA directly.
In some cases, the presence of a small effector molecule may increase transcription
● These molecules are termed inducers
● They function in two ways:
1. Bind to an activator protein and cause them to bind to DNA
2. Bind to a repressor protein and prevent it from binding to DNA
● Genes that are regulated in this manner are termed inducible.
In other cases, the presence of a small effector molecule can decrease transcription.
● Corepressors bind to repressor proteins and cause them to bind to DNA
● Inhibitors bind to activator proteins and prevent them from binding to DNA
● Genes that are regulated in this manner are termed repressible genes
Regulatory proteins have two binding sites
● One for a small effector molecule
● The other for DNA
, Regulation of the lac operon
At the turn of the 20th century, scientists made the following observation.
● A particular enzyme appears in the cell only after the cell has been exposed to the enzyme’s substrate
● This observation became known as enzyme adaptation
Francois Jacob and Jacques Monod at the Pasteur institute in Paris were excited by this phenomenon.
● They focused their attention on lactose metabolism in E. coli to investigate this problem: regulation of Lac operon
An operon is a regulatory unit consisting a few structural genes under the control of one promoter and one terminator
● It encodes a polycistronic (poly-ORF) mRNA that contains the coding sequence for two or more structural proteins
● This allows a bacterium to coordinately regulate a group of genes that encode proteins involved in the same
process/function
An operon contains several different regions
● Promoter: operator; terminator; structural genes;
Not all genes in bacteria are in operons
Operons involved in catabolism (breakdown of a substance) are typically inducible → e.g. Lac Operon
● The substance to be broken down acts as the inducer
Figure 14.3a shows the organization and transcriptional regulation of the lac operon genes.
There are two distinct transcriptional units
1. The actual lac operon contains:
a. DNA elements involved in transcriptional regulation
● Promoter à bound by RNA polymerase
● operator à bound by the lac repressor protein
● CAP site à bound by the catabolite activator protein
(CAP)
b. Structural genes contain the coding sequence for the
enzymes
● LacZ à encodes beta-galactosidase
→ enzymatically cleaves lactose and lactose analogous
→ also converts lactose into allolactose
● LacY à encodes lactose permease
→ membrane protein required for transport of lactose
and analogous
● LacA à encodes transacétylase
→ covalently modifies lactose and analogous
→ suggested to help detoxification caused by excess lactose/analogous by
preventing their cellular re-entry
2. The lacl gene codes for a regulatory protein à repressor
● Not considered part of the lac operon
● has its own promoter, the i promoter
● constitutively expressed at fairly low levels
● encodes the lac repressor
● the lac repressor protein functions as a homo-tetramer
● Only a small amount of protein is needed to repress the lac operon
→ there are usually 10 tetramers per cell
Gene regulation in Bacteria
Summary
Transcriptional regulation
The term gene regulation means that the level of gene expression can differ under particular conditions.
Genes that are unregulated are termed constitutive.
● They are constantly expressed
● Frequently, constitutive genes encode proteins that are frequently crucial for the survival of the cell/organism →
expressed in all cell types
The benefit of regulating genes is that encoded proteins/RNAs will be produced only when required.
Gene regulation is important for cellular processes such as
1. Metabolism
2. Response to environmental stress
3. Cell division
4. Differentiation and development
5. Several other reasons (cell fitness etc.)
Regulation of gene expression:
1. Transcription – Gene → mRNA
2. Translation – mRNA → protein
3. Post translation – Protein → functional protein
It is essential to study this process in prokaryotes because some of them are still an issue for our health. With the knowledge of
the study, we can have more treatments.
The most frequent way to regulate gene expression in bacteria is at the transcription initiation level
● The rate of mRNA production can be increased or decreased
Transcriptional regulation involves the actions of two main types of regulatory proteins
● Repressors → Bind directly or indirectly to DNA and inhibit transcription: negative control
● Activator → Bind directly or indirectly to DNA and increase transcription: positive control
Small effector molecules influence transcription regulation
● Small effector molecules are sometimes called ligands → short peptides (hormones, neurotransmitters, etc.),
metabolites, drugs …
● These bind to regulatory proteins and not to DNA directly.
In some cases, the presence of a small effector molecule may increase transcription
● These molecules are termed inducers
● They function in two ways:
1. Bind to an activator protein and cause them to bind to DNA
2. Bind to a repressor protein and prevent it from binding to DNA
● Genes that are regulated in this manner are termed inducible.
In other cases, the presence of a small effector molecule can decrease transcription.
● Corepressors bind to repressor proteins and cause them to bind to DNA
● Inhibitors bind to activator proteins and prevent them from binding to DNA
● Genes that are regulated in this manner are termed repressible genes
Regulatory proteins have two binding sites
● One for a small effector molecule
● The other for DNA
, Regulation of the lac operon
At the turn of the 20th century, scientists made the following observation.
● A particular enzyme appears in the cell only after the cell has been exposed to the enzyme’s substrate
● This observation became known as enzyme adaptation
Francois Jacob and Jacques Monod at the Pasteur institute in Paris were excited by this phenomenon.
● They focused their attention on lactose metabolism in E. coli to investigate this problem: regulation of Lac operon
An operon is a regulatory unit consisting a few structural genes under the control of one promoter and one terminator
● It encodes a polycistronic (poly-ORF) mRNA that contains the coding sequence for two or more structural proteins
● This allows a bacterium to coordinately regulate a group of genes that encode proteins involved in the same
process/function
An operon contains several different regions
● Promoter: operator; terminator; structural genes;
Not all genes in bacteria are in operons
Operons involved in catabolism (breakdown of a substance) are typically inducible → e.g. Lac Operon
● The substance to be broken down acts as the inducer
Figure 14.3a shows the organization and transcriptional regulation of the lac operon genes.
There are two distinct transcriptional units
1. The actual lac operon contains:
a. DNA elements involved in transcriptional regulation
● Promoter à bound by RNA polymerase
● operator à bound by the lac repressor protein
● CAP site à bound by the catabolite activator protein
(CAP)
b. Structural genes contain the coding sequence for the
enzymes
● LacZ à encodes beta-galactosidase
→ enzymatically cleaves lactose and lactose analogous
→ also converts lactose into allolactose
● LacY à encodes lactose permease
→ membrane protein required for transport of lactose
and analogous
● LacA à encodes transacétylase
→ covalently modifies lactose and analogous
→ suggested to help detoxification caused by excess lactose/analogous by
preventing their cellular re-entry
2. The lacl gene codes for a regulatory protein à repressor
● Not considered part of the lac operon
● has its own promoter, the i promoter
● constitutively expressed at fairly low levels
● encodes the lac repressor
● the lac repressor protein functions as a homo-tetramer
● Only a small amount of protein is needed to repress the lac operon
→ there are usually 10 tetramers per cell
