Zusammenfassung der Ressource
Eukaryotic Gene Regulation
- Key Points
- GR- the process of
controlling which
genes in a cell's DNA
are expressed.
- Used to make a
functional
product; such as
a protein.
- Different cells in
multicellular
organisms may
express very different
sets of genes, even
though they contain
the same DNA
- The set of genes
expressed in a
celldetermines the
set of proteins and
functional RNAs it
contains.
- This gives it it's
unique properties
- In eukaryotes, like
humans, gene
expression involves
many steps, and gene
regulation can occur
at any of these steps.
- However, many
genes are regulated
primarily at the
level of
transcription.
- Gene regulation makes cells
different.
- GR is how a cell controls which
of it's many genes, within it's
genome are "turned on"
(expressed).
- Due to GR each cell
type within the body
has a different set
of active genes.
- Despite the fact that almost all the
cells in your body contain the exact
same DNA
- These different
patterns of gene
expression cause your
various cell types to
have different sets of
proteins, making each
cell uniquely specialized
to do it's job
- For example, one of the jobs of the live is to remove toxic
substances like alcohol from the bloodstream. To do this, liver cells
express genes encoding subunits of an enzyme called alcohol
dehydrogenase. This enzyme breaks alcohol down into a non-toxic
molecule. The neurons in a person's brain don't remove toxins
from the body, so they keep these genes unexpressed.
- Similarly the cells of the liver don't send signals using
neurotransmitters, so they keep their
neurotransmitter genes unexpressed.
- There are many other genes that are ezpressed
differently between liver cells and neurones (or any
two cell types in a multicellular organism like
yourself)
- How do cells "decide" which genes to turn on?
- Many factors that can affect
which genes a cell expresses.
- Different cell types express different sets of genes.
However, two different cells of the same type may
also have different gene expression patterns
depending on their environment and internal state.
- A cell's gene expression pattern is
determined by information from
both inside and outside the cell.
- Examples of information inside the
cell: the proteins it inherited from it's
mother cell, whether its DNA is
damaged, and how much ATP it has.
- Examples of information outside the cell: chemical signals
from other cells, mechanical signals from the extracellular
matrix, and nutrient levels.
- Cells have molecular pathways that convert
information - such as the binding of a chemical signal
to its receptor - into a change in gene expression.
- E.G - A growth factor is a chemical signal from
a neighboring cell that instructs a target cell to
grow and divide. The cell "notices" the growth
factor and "decides" to divide.
- The cell detects the growth factor
through physical binding of the
growth factor to a receptor protein
on the cell surface.
- Binding of the growth factor causes
the receptor to change shape,
triggering a series of chemical
events in the cell that activate
proteins called transcription factors
- The transcription factors bind to
certain sequences of DNA in the
nucleus and cause transcription of
cell division-related genes.
- The products of these genes are
various types of proteins that make
the cell divide. (Drice cell growth
and/or push the cell forward in the
cell cycle)
- Growth factor signalling is complex and
involves the activation of a variety of targets,
including both transcription factors and
non-transcription factor proteins.
- Gene expression can be regulated at many stages
- Gene expression involves many steps and almost all of them can be regulated.
- Chromatin accessibility - The
structure of chromatin (DNA and
its organizing proteins) can be
regulated. More open or "relaxed"
chromatin makes a gene more
available for transcription.
- Transcription - a key regulatory point for many
genes. Sets of transcription factor proteins bind to
specific DNA sequences in or near a gene and promote
or repress its transcription into an RNA
- RNA Processing - Splicing,
capping and addition of a
poly-A tail to an RNA
molecule can be regulated,
and so can exit from the
nucleus. Different mrNAs
may be made from the
same pre-mRNA by
alternative splicing.
- RNA Stability - The lifetime of an mRNA
molecule in the cytosol affects how
many proteins can be made from it.
Small regulatory RNAs called miRNAs
can bind to target mRNAs and cause
them to be chopped up.
- Translation - \translation of an mRNA
may be increased or inhibited by
regulators. For instance, miRNAs
sometimes block translation of their
target mRNAs (rather than causing
them to be chopped up)
- Protein activity - Proteins can undergo a variety
of modifications, such as being chopped up or
tagged with chemical groups. These
modifications can be regulated and may affect
the activity or behavior of the protein.
- Although all stages of gene expression can be
regulated, the main control point for many
genes is transcription. Later stages of
regulation often refine the gene expression
patterns that are "roughed out" during
transcription.
- Bacterial Gene Regulation
- Key
Points
- Bacterial genes are often found in
operon. Genes in an operon are
transcribed as a group and have a
single promoter.
- Each operon contains regulatory DNA
sequences, which act as binding sites for
regulatory proteins that promote or
inhibit transcription.
- Regulatory proteins often bind to
small molecules, which can make
the protein active or inactive by
changing its ability to bind to DNA.
- Some operons are inducible, meaning they
cn be turned on by the presence of a
particular small molecule. Others are
repressible, meaning that they are on by
default but can be turned off by a small
molecule.
- Introduction
- The bacteria in your gut or between
your teeth have genomes that
contain thousands of different
genes. Mos of these gense encode
proteins, each with its own role in a
process such as fuelling
metabolism, maintenance of cell
structure, and defense against
viruses.
- Some of these proteins are needed
routinely, while others are needed only
under certain circumstances. Thus, cells
don't express all the genes in their
genome all the time.
- You can think of the genome as
being like a cookbook with many
different recipes in it. The cell will
only use the recipes (express the
genes) that fit its current needs.
- How is Gene Expression regulated?
- There are various forms of gene
regulation, that is, mechanisms for
controlling which genes get expressed
and at what levels. However, a lot of
gene regulation occurs at the level of
transcription
- Bacteria have specific regulatory
molecules that control whether a
particular gene will be transcribed
into mRNA.
- Often, these molecules
act by binding to DNA
near the gene and
helping or blocking the
transcription enzyme,
RNA polymerase.
- In bacteria. genes are found in Operons.
- Related genes are often found in a
cluster on the chromosome where
the are transcribed from one
promoter (RNA Polymerase binding
site) as a single unit. Such a cluster
of genes is under control of a single
promoter known as an operon.
- Operons are common in
bacteria, but they are
rare in eukaryotes, such
as humans.
- In general, an operon will contain
genes than function in the same
process.
- For example, a well studied operon called the
lac operon contains genes that encode proteins
involved in uptake and metabolism of a
particular sugar, lactose..
- Operons allow the cell to
efficiently express sets of
genes whose products are
needed at the same time.
- Anatomy of an Operon
- Operons aren't just made up
of the coding sequences of
genes. Instead they also
contain regulatory DNA
sequences that control
transcription of the operon.
Typically, these sequences
are binding sites for
regulatory [roteins, which
control how much the
operon ins transcribed.
- The promoter, or the
site where RNA
polymerase binds, is
one example of a
regulatory DNA
sequence.
- Most operons have other
regulatory DNA sequences
in addition to the
promoter. These
sequences are binding
sites for regulatory
proteins that turn
expression of the operon
"up" or "down".
- Some regulatory proteins are
called repressors that bind to
pieces of DNA called operators.
When bound to its operator, a
repressor reduces transcription
(e.g by blocking RNA
polymerase from moving
forward on the DNA)
- Some regulatory proteins are
activators. When an activtor is
bound to a DNA binding site, it
increases transcription of the
operon (e.g by helping RNA
polymerase bind to the
promoter).
- Regulatory proteins are
produced within an
organism, they are encoded
by genes in the bacteruim's
genome. The genes that
encode regulatory proteins
are sometimes called
regulatory genes.
- Many regulatory proteins can themselves be
turned "on" or "off" by specific small molecules. The
small molecule binds tot he protein, changing its
shape and altering its ability to bind to DNA. For
instance, an activator may only become active
(able to bind to DNA) when it's attachedto a
certain small molecule.
- Operons may be inducible or repressible.
- Some operons are
usually "off", but can be
turned "on" by a small
molecule. The molecule
is called an inducer, and
the operon is said to be
inducible.
- For example, the lac operon is
an inducible operon that
encodes enzymes for
metabolism of lactose. It only
tirns on when the sugar is
present. The inducer in this
case is allolactose, a modified
form of lactose.
- Some operons are usually "on",
but can be turned "off" by a small
molecule. The molecule is called a
coressor, and the operon is said to
be repressible.
- For example the trp operon is a
repressible operon that encodes
enzymes for synthesis of the amino
acid tryptophan. This operon is
expressed by default, but can be
repressed when high levels of thr
amino acid tryptophan is present. The
corepressor in this case is tryptophan
- Gene Regulation differences between Species
- Differences in gene regulation makes the
different cell types in a multicellular organism
unique in structure and function.
- Gene regulation can also help us
explain some of the with differences
in form and function between
different species relatively similar
gene sequences.
- Human and chimpanzees have
genomes that are about 98% identical
at the DNA level. Thee protein-coding
sequences are different between
human and chimpanzees, contributing
to the differences between the
species.
- However, researchers also think that changes in gene
regulation play a major role in making humans and chimps
different from one another. For instance, some DNA regions
are present in the chimpanzee genome but missing in the
human genome, contain known gene regulatory sequences
that control when, where or how strongly a gene is expressed.