Download Bis2A 9.0 Introduction to Gene Regulation

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Bis2A 9.0 Introduction to Gene
Regulation
∗
The BIS2A Team
This work is produced by OpenStax-CNX and licensed under the
Creative Commons Attribution License 4.0†
Section Summary
Regulation is all about decision making. The subject of gene regulation is all about studying how and when
cells make decisions about which genes to turn on, turn o or to turn up or down. In the following section
we discuss some of the fundamental mechanisms and principles used by cells to regulate gene expression in
response to changes in cellular or external factors. This biology is important for understanding how cells
adjust changing environments, including how some cells decide to become specialized for certain functions
(e.g. tissues) in a multicellular organism.
1 Gene Expression
Whether they are unicellular or in a multi-cellular organism, all cells control when and how much each of
its genes are expressed. For this to occur, there must be sensory and control mechanisms that monitor the
environment and help transmit this information to the genome in a way that allows for decisions about gene
expression to be made.
note:
time?
Why is it important to regulate gene expression? Why not just express all genes all of the
Create a list of reasons why gene expression is necessary for a single celled microbe. Create
a list of reasons why gene expression is necessary for a multicellular organism. (Some parts of your
lists will overlap.)
note:
The process of gene expression requires multiple steps depending on what the fate of the nal product will
be. In the case of structural and regulatory RNAs (i.e. tRNA, rRNA, snRNA, etc.) the process requires
that a gene be transcribed and that any needed post-transcriptional processing take place. In the case of a
protein coding gene, the transcript must also be translated into protein and if required, modications to the
protein must also be made. Of course, both transcription and translation are multi-step processes and most
those sub-steps are also potential sites of control. While many regulatory mechanisms exist, we will focus
primarily on developing a working understanding of the basic mechanisms for regulating the initial steps of
transcription.
∗ Version
1.1: Feb 27, 2016 12:27 am -0600
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1.1 Eukaryiotic vs Prokaryotic Gene Regulation
Figure 1
1.2 Activation and Repression of Gene Expression
Expression of the gene
There are three states that can be used to described the expression of a gene or operon. The rst is called
constitutive1 expression. Constitutive expression is the level of transcription that happens regardless of
need - it refers to the unregulated level of gene expression. If the promoter is strong, the constitutive expression can be very high while if the promoter is weak constitutive expression levels could be very low.
The second state is activated or induced expression. Under a specic set of conditions, if the expression of a gene or operon is increased it is said to be activated. Gene activation results in an increase in
amount of mRNA produced from a gene after some environmental signal has been received.
Finally, expression of a gene can be decreased under a certain set of conditions. This is called
and a gene responding in the manner is said to be repressed.
repres-
sion
Mechanistically, in activation and repression, regulatory proteins are required to change the expression
pattern of the gene being observed. If the regulatory protein acts (by binding DNA) in a way that increases
expression then it is considered an activator. If the regulatory protein acts (by binding DNA) to repress or
decrease expression of the gene then it is considered a repressor. Activators and repressors fall into a larger
category of proteins called transcription factors, proteins that assemble at the promoter to regulate the
initiation activity of the RNA polymerase.
It is worth noting that the terms activator and repressor describe in many instances idealized cases. A
number of transcription factors may act to activate gene expression in some contexts while repressing in other
contexts. Some transcription factors will simply act to modulate expression (either up or down depending
on context). Some of your instructors prefer to avoid using the terms activator and repressor and instead
1 http://dictionary.reference.com/browse/constitutive
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prefer to simply discuss the activity of transcription various transcription factors as either a positive or a
negative inuence on gene expression in specic cases. If the terms are used you might hear your instructor
saying that the transcription factor in question ACTS LIKE/AS a repressor or that it ACTS LIKE/AS an
activator taking care not to call it simply an activator or repressor.
What types of interactions do you think happen between the amino acids of the transcription
factor and the double helix of the DNA? How do transcription factors recognize their binding site
on the DNA?
note:
At this point in the class we have discussed many 'sites' on the DNA. What is a DNA site
and which ones have we discussed thus far? What binds to these sites?
note:
Figure 2: Transcription factors (TFs) act to alter gene expression. They can activate (enhance) gene
expression or repress (lower) gene expression. Each TF will bind to its own specic site on the DNA.
Some TFs have only a few sites in the genome, some TFs are more widely used and can have hundreds
of binding sites in the genome.
Source: modied from https://www.studyblue.com/notes/note/n/exam-1/deck/3866722
A simple test
So how does one determine if a regulatory protein functions in a positive or negative way? A simple genetic
test is to ask "what happens to expression if the regulatory protein is absent?" If a regulatory protein is acting
positively, then its presence is required to activate gene expression. In its absence, there is no regulatory
protein, therefore no activation, and the outcome is no transcription. The opposite is true for a regulatory
protein acting negatively. In its absence expression should be increased, because the gene keeping expression
low is no longer around.
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Allosteric Modulators of Regulatory Proteins
The activity of many proteins, including regulatory proteins and various transcription factors can be allosterically regulated by the abundance of small molecules in the cell. These small molecules are often referred to
as inducers or co-repressors or co-activators and are often metabolites, such as lactose or tryptophan
or small regulatory molecules, such as cAMP or GTP. In the next few modules we will go over examples of
regulatory systems that are controlled by allosterically regulated repressor and activator proteins.
Exercise 1
(Solution on p. 5.)
Bacteria and archaea lack a nucleus. Therefore, the genes in bacteria and archaea are:
a.
b.
c.
d.
all expressed, all of the time
transcribed and translated almost simultaneously
transcriptionally controlled because translation begins before transcription ends
b and c are both true
Exercise 2
(Solution on p. 5.)
Describe how controlling gene expression will alter the overall protein levels in the cell.
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Solutions to Exercises in this Module
to Exercise (p. 4)
D
to Exercise (p. 4)
The cell controls which proteins are expressed and to what level each protein is expressed in the cell.
Prokaryotic cells alter the transcription rate to turn genes on or o. This method will increase or decrease
protein levels in response to what is needed by the cell. Eukaryotic cells change the accessibility (epigenetic),
transcription, or translation of a gene. This will alter the amount of RNA and the lifespan of the RNA
to alter the amount of protein that exists. Eukaryotic cells also control protein translation to increase or
decrease the overall levels. Eukaryotic organisms are much more complex and can manipulate protein levels
by changing many stages in the process.
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