This module on gene expression is derived from a week long course called, "A Librarian's
Guide to NCBI," which took place in April 2013 at the National Library of Medicine.
These are introductory lectures, suitable for beginning or intermediate users of NCBI
resources and for those with little background in molecular biology.
We've split this module into 3 separate videos, Parts 1, 2 and 3.
At the end of Parts 1 and 2 you can click on a note to open the next video in a new
window.
I'm not going to read this table of contents, so if you want more time on this slide, use
the video's pause function.
I'll start with the simple statement that nearly every cell in an organism has a complete
set of genes.
However, gene expression varies temporally and spatially, for example, the genes expressed
in the skin at a given point in time are different from those expressed in say, your liver.
Gene expression also varies during development, and is changed by disease or, going in the
opposite direction, altered gene expression may itself result in disease.
Even environmental factors can influence gene expression.
I'm going to talk more about the concept of gene expression, but I will use an analogy
to the real biological scenario.
First, when we think about genes, we are most likely to think about the protein coding genes.
And rightly so: proteins are the cell's workers, performing most of the cell's functions.
So, let's think about cells as powerhouses.
By analogy we can think about the protein coding genes as appliances.
They come in pairs, one from each parent, and color differences indicate variation in
the gene's sequence; gene alleles, if you are familiar with that term.
Take this mixer: when it works, it is on it makes dough, the mRNA, which is then translated
into cookies, the protein.
However, the genome is much more than the protein coding genes.
For an appliance to work, outlets, wires, and switches have to be available, and someone
has to plug it in and turn it on or off.
So that brings us to the concept of gene regulation...
...the outlets, switches and wire.
In biological terms, these are called functional elements, which include genes that encode
a variety of regulatory RNAs -- short RNAs that help control gene expression -- as well
as other non-coding sequences, such as enhancers and promoters, which act as binding sites
for proteins called transcription factors that affect a gene's expression.
Let's add these regulators -- wires, outlets and switches -- to our sytlized genome.
But we're not quite finished...
We've addressed this first statement...But, we also know that the genome is more than
just the DNA sequence; there is another layer to the genome called the epigenome.
Let's look at some epigenomic, also called epigenetic, factors: The first is DNA methylation,
where the sequence itself does not change, but cytosine residues, primarily, are chemically
modified by enzymes that add a methyl group.
This usually turns off, or silences, the gene, meaning that it can not be expressed.
Another level of epigenomic regulation is the chromatin structure.
Our view of human chromosomes is often like the image I showed earlier with 23 pairs of
tightly coiled chromosomes.
However, this is only during a stage of cell division where DNA is the most condensed.
When genes are active, the DNA is less tightly coiled and often referred to as open chromatin.
One regulator of chromatin structure is the modification of proteins called histones.
DNA is wrapped around histones and, similar to methylation of cytosine residues, histone
amino acids can be chemically modified in ways that change the protein's interaction
with DNA.
And it is important to note that epigenomic factors can be inherited.
If you want to learn more, we have a nice primer on the Epigenomics database home page.
OK, let's explore a bit more about regulation of gene expression.
We'll continue with our analogy.
The gist is that regulation ocurrs through complex pathways and regulatory networks.
Numerous proteins are interacting with each other, and directly with DNA, to orchestrate
the timing of expression for an individual gene.
If you want to see some examples, try this search in the Biosystems database.
I will now return to our cell analogy, to the powerhouse, to see how this all fits together.
Here, I am illustrating just two protein coding genes, a mixer and a blender.
The decision was made, through regulatory pathways, that the timing was not right for
the blender gene, but was right for the mixer gene.
However, only one allele of the mixer gene gets expressed; the other one is silenced,
say by a methyltransferase.
Perhaps this methylation was already in the parent who contributed the allele.
That's the end of Gene Expression Part 1.
We'll next turn our attention to how gene expression is studied.
Click on the note to open the Part 2 video in a new window.