2. Differential Gene Expression
• All our somatic cells have the same genetic information. This is known as genetic
equivalence
• Yet how is hemoglobin make in only red blood cells? Why does your stomach not grow
hair if the genes are there?
• The answer is that although each cell has all the genes, they are not all turned on.
Different cells activate different genes.
• This is what differentiates our cells
3. What is
differential
gene
expression
• There are three ideas behind this:
• Genetic equivalence
• Unused genes stay around to potentially be
expressed later
• Only a small percentage of the genome is
expressed in each cell
4. The Central Dogma of Biology
• Before we continue, let’s review the central dogma of biology
• Proteins determine all your phenotypes
• Things like eye color, your height, insulin production, pretty much everything
• Proteins are made from Amino Acids. If proteins are chains, amino acids are the links
• The sequence of amino acids will determine what type of protein it will be
• The instructions for the amino acid order is in your genes, which are located in your DNA
• In particular, the DNA is made of bases. The order of these bases determine which amino acid to
use
• In summary: DNA base order > Amino Acid Order > Type of Protein > Your Traits
5. The Central Dogma of
Biology (continued)
DNA is found only in the nucleus of the cell. It doesn’t leave
Ribosomes (which make proteins) are only found in the cytoplasm
Therefore, RNA goes into the nucleus, unzips it, and transcribes the
base pairs
It then brings that transcript out to the ribosome where it is
translated into the different amino acids that will make the protein
The next slide repeats this slide but with more detail.
6. The Central
Dogma of
Biology
(continued)
Pre-mRNA is taken from a strand of DNA
Pre-mRNA removes non-coding parts and protects the ends of
the strand this then becomes a molecule or mRNA (messenger
RNA). This is transcription
mRNA leaves the nucleus and migrates to the ribosomes. It gives
out a codon (three bases) which code for a certain amino acid
(this is translation). The amino acids make the protein
The protein then needs to be folded a certain way and probably
modified before its finally finished
7. Regulation of Gene Expression
• Now that we explained the main idea behind making proteins, how can gene expression
be regulated? It happens at four levels:
• 1) Differential Gene Transcription- this determines which genes will be transcribed to
RNA (pre-mRNA to be exact)
• 2) Selective Pre-mRNA Processing- This is going to determine which parts of the
transcribed RNA can enter the cytoplasm and officially become mRNA
• 3) Selective mRNA Translation- This will determine which of the mRNA in the
cytoplasm can be translated into proteins
• 4) Differential Posttranslational Protein Modification- this determines which proteins
will function in the cell
• These are the essentially the levels discussed in the previous slide
8. Anatomy of the
Gene
• A nucleus of a cell contain Chromatin
• Chromatin contain DNA and protein (histones)
• The DNA is wrapped around the histones
sometimes lightly and sometimes tightly.
• Euchromatin- loosely condensed and can be
transcribed
• Heterochomatin- tightly condensed and not
typically transcribed
• The DNA wrapped in the histones is called a
nucleosome
• The nucleosomes are then coiled into a solenoid
• This is sometimes referred to as “beads on a string”
9. Exons and
Introns
• A strand of nucleic acid is not continuously
coded for proteins. There are segments that
are “useful” and some that are not
• Exons are the part of a strand that codes
for a protein
• Introns do not code for a particular amino
acid sequence
• These are two of many regions of a strand
10. • Notice the difference between
pre-mRNA segment and the
mRNA segment below it.
• The introns were spliced out.
• You can also see how the
promoter region is missing in the
pre-mRNA versus the DNA
segment at the top
11. Noncoding regulatory elements
• Transcription Factors- proteins that ensure the code from the DNA is copied to RNA. It ensures that the
right genes are expressed.
• Promoters- the part of the gene where transcription is started. RNA Polymerase is the enzyme that
handles this
• Enhancers- as the name implies, the enhance the rate of transcription. They do this by binding to
transcription factors. It links its part of the gene to the promoter.
• It doesn’t need to be near by. It can fold the DNA segment, so the two areas are near each other.
• Silencers- They decrease transcription activity
12. • Notice that in photo B the strand
was bent so that the enhancer
could get closer to the promoter
• They need to both be on the same
strand, but they don’t need to be
close to each other.
• So different genes for a trait don’t
have to be all lined up.
13. Mechanisms
of Differential
Gene
Expression There are two that are common:
Epigenetic
Modification of
Chromatin
Control Through
Transcription Factors
Out of the four levels at which gene
expression can be regulated, most of
the mechanisms involve regulating how
the gene is transcribed to pre-mRNA.
14. Epigenetic Modification
• Epigenetics is where the phenotype changes because of how a gene is expressed
• The genetic material is not changing, just how it is expressed
• Recall that how tightly DNA is wrapped around a histone influences its translation to RNA
(mRNA).
• There are chemicals that can loosen or tighten the nucleosome. This effects gene expression.
• The patterns of the chemicals responsible for this (like acetyl and methyl groups) are
inheritable because they can be remembered.
16. Transcription Factors
Transcription factors are grouped into families. They specialize in
different functions.
• For example, the HOX family transcription factor is responsible for axis formation in an
embryo
Transcription factors:
• Recruit different histone-modifying enzymes which effect how loose or tight they are
wrapped up. This effects expression
• They stabilize RNA polymerase activity
• They coordinate the timing for RNA expression
18. Control of
RNA
Expression
by
Cytoplasmic
Localization
• The RNA goes out to the cytoplasm to find the
ribosomes. Where in the cytoplasm it goes
matters.
• Diffusion and Local Anchoring- proteins in
the cytoplasm trap the mRNA
• Localized Protection- proteins protect the
mRNA in just one place in the cytoplasm
• Active Transport Along the Cytoskeleton-
mRNA rides along microtubules
19. Posttranslational
Protein
Modification
Even when a protein is made, this is not
necessarily the end
Sometimes certain parts of the protein
must be cleaved away first
They may need to attach to another
protein or an ion like calcium
Perhaps a functional group needs to be
added or removed