Gene regulation in eukaryotes
Gene Gene regulation is necessary to ensure
regulation 1. Expression of genes in an accurate pattern during the various developmental stages of the life
cycle
1. Some genes are only expressed during embryonic stages, whereas others are only expressed in the
adult
2. Differences among distinct cell types; Nerve and muscle cells look so different because of gene
regulation rather than differences in DNA content
3. Homeostasis; Regulation of the cell’s regular internal functions
4. Optimal response to changes in nutrient availability, and environmental changes and stresses
Almost every step involved in gene expression is controlled.
Transcription Transcription factors are proteins that influence the ability of RNA polymerase to transcribe a given gene.
factors There are two main types
General transcription factors: Required for the binding of the RNA pol to the core promoter and its
progression to the elongation stage: Are necessary for basal transcription
Regulatory transcription factors: Serve to regulate
the rate of transcription of nearby genes. They
influence the ability of RNA pol to begin transcription
of a particular gene. Regulatory transcription factors
recognize cis regulatory elements located near the
core promoter. These sequences are known as
response elements, control elements, regulatory
elements, or cis-acting elements. The binding of
these proteins to these elements, affects the
transcription of an associated gene.
A regulatory protein that increases the rate of
transcription is termed an activator. Promoter
contain various binding sites >> one is ‘enhancer’
A regulatory protein that decreases the rate of
transcription is termed a repressor.
Most Eukaryotic genes are regulated by many factors. This is
known as combinatorial control.
RTF Transcription factor proteins contain regions, called domains, that have specific functions. One domain
could be for DNA-binding. Another domain could bind to other transcription factors. Yet another could
provide a binding site for effector molecules. A ‘motif’ usually refers to series of contiguous secondary
structures the domain consist of. Domain/ portion of a domain has a very similar structure in many
different proteins. Structurally similar regions = motifs. a-helix has proper width to bind into the major
groove.
Enhancers and The binding of a transcription factor to an enhancer increases the rate of transcription: up-regulation can
silencers be 10- to 1,000-fold
The binding of a transcription factor to a silencer decreases the rate of transcription: down-regulation
Many response elements, including enhancer, are orientation independent and bidirectional, but only
when they are at a sufficiently large distance from the core promoter, the TSS. They can function in the
, forward or reverse orientation
Most response elements are located within a few hundred nucleotides upstream of the promoter.
However, some are found at various other sites; Several thousand nucleotides away, downstream from the
promoter, even within introns!
GTFs: TFIID Most regulatory transcription factors do not bind directly to RNA polymerase: They do it indirectly.
and mediator Two common protein complexes that communicate the effects of regulatory transcription factors are
1. TFIID: = protein complex, multiple (20) subunits
2. Mediator: protein complex, multiple subunits
TFIID TFIID binds to TATA box and is needed to recruit RNA pol II to the corepromoter.
- Activator proteins can enhace ability of TFIID to initiate transcription: activator helps TFIID to bind
to TATA-box and/or enhances function of TFIID to recruit RNA pol II. DNA-binding TF (activators)
can interact with GTF via coactivator.
- Repressors inhibit function of TFIID by preventing the binding of TFIID to TATA-box or inhibit ability
of TFIID to recruit RNA pol II to the core promoter.
Mediator RTF’s control RNA pol II via mediator. Mediator controls the ability of RNA pol to progress to elongation
stage of transcription via phosporylation of carboxyl-terminal domain (CTD).
- Transcriptional activator
stimulates the function of
mediator. This enables RNA pol
to form a preinitiation complex
(PIC). It then proceeds to the
elongation phase of transcription
- Transcriptional repressor inhibits
the function of mediator.
Transcription is repressed.
The functions There are three common ways that the
of RTF can be function of regulatory transcription
modulated factors can be affected
1. Binding of a small effector
molecule/ ligands
2. Protein-protein interactions
3. Covalent modification of the
protein
Steroid Regulatory transcription factors that respond to steroid hormones are termed steroid receptors. The
hormones and hormone actually binds to the transcription factor. The ultimate action of a steroid hormone is to affect
RTFs gene transcription. Steroid hormones are produced by endocrine glands. Secreted into the bloodstream.
Then taken up by cells that respond to the hormone.
Gene Gene regulation is necessary to ensure
regulation 1. Expression of genes in an accurate pattern during the various developmental stages of the life
cycle
1. Some genes are only expressed during embryonic stages, whereas others are only expressed in the
adult
2. Differences among distinct cell types; Nerve and muscle cells look so different because of gene
regulation rather than differences in DNA content
3. Homeostasis; Regulation of the cell’s regular internal functions
4. Optimal response to changes in nutrient availability, and environmental changes and stresses
Almost every step involved in gene expression is controlled.
Transcription Transcription factors are proteins that influence the ability of RNA polymerase to transcribe a given gene.
factors There are two main types
General transcription factors: Required for the binding of the RNA pol to the core promoter and its
progression to the elongation stage: Are necessary for basal transcription
Regulatory transcription factors: Serve to regulate
the rate of transcription of nearby genes. They
influence the ability of RNA pol to begin transcription
of a particular gene. Regulatory transcription factors
recognize cis regulatory elements located near the
core promoter. These sequences are known as
response elements, control elements, regulatory
elements, or cis-acting elements. The binding of
these proteins to these elements, affects the
transcription of an associated gene.
A regulatory protein that increases the rate of
transcription is termed an activator. Promoter
contain various binding sites >> one is ‘enhancer’
A regulatory protein that decreases the rate of
transcription is termed a repressor.
Most Eukaryotic genes are regulated by many factors. This is
known as combinatorial control.
RTF Transcription factor proteins contain regions, called domains, that have specific functions. One domain
could be for DNA-binding. Another domain could bind to other transcription factors. Yet another could
provide a binding site for effector molecules. A ‘motif’ usually refers to series of contiguous secondary
structures the domain consist of. Domain/ portion of a domain has a very similar structure in many
different proteins. Structurally similar regions = motifs. a-helix has proper width to bind into the major
groove.
Enhancers and The binding of a transcription factor to an enhancer increases the rate of transcription: up-regulation can
silencers be 10- to 1,000-fold
The binding of a transcription factor to a silencer decreases the rate of transcription: down-regulation
Many response elements, including enhancer, are orientation independent and bidirectional, but only
when they are at a sufficiently large distance from the core promoter, the TSS. They can function in the
, forward or reverse orientation
Most response elements are located within a few hundred nucleotides upstream of the promoter.
However, some are found at various other sites; Several thousand nucleotides away, downstream from the
promoter, even within introns!
GTFs: TFIID Most regulatory transcription factors do not bind directly to RNA polymerase: They do it indirectly.
and mediator Two common protein complexes that communicate the effects of regulatory transcription factors are
1. TFIID: = protein complex, multiple (20) subunits
2. Mediator: protein complex, multiple subunits
TFIID TFIID binds to TATA box and is needed to recruit RNA pol II to the corepromoter.
- Activator proteins can enhace ability of TFIID to initiate transcription: activator helps TFIID to bind
to TATA-box and/or enhances function of TFIID to recruit RNA pol II. DNA-binding TF (activators)
can interact with GTF via coactivator.
- Repressors inhibit function of TFIID by preventing the binding of TFIID to TATA-box or inhibit ability
of TFIID to recruit RNA pol II to the core promoter.
Mediator RTF’s control RNA pol II via mediator. Mediator controls the ability of RNA pol to progress to elongation
stage of transcription via phosporylation of carboxyl-terminal domain (CTD).
- Transcriptional activator
stimulates the function of
mediator. This enables RNA pol
to form a preinitiation complex
(PIC). It then proceeds to the
elongation phase of transcription
- Transcriptional repressor inhibits
the function of mediator.
Transcription is repressed.
The functions There are three common ways that the
of RTF can be function of regulatory transcription
modulated factors can be affected
1. Binding of a small effector
molecule/ ligands
2. Protein-protein interactions
3. Covalent modification of the
protein
Steroid Regulatory transcription factors that respond to steroid hormones are termed steroid receptors. The
hormones and hormone actually binds to the transcription factor. The ultimate action of a steroid hormone is to affect
RTFs gene transcription. Steroid hormones are produced by endocrine glands. Secreted into the bloodstream.
Then taken up by cells that respond to the hormone.
