Video Transcript
In this video, we’ll learn more
about DNA in eukaryotes and what the terms chromosome, chromatin, and nucleosome
mean. We’ll learn about how DNA could be
compacted with histone proteins to form chromosomes. And we’ll see how chromosomes
appear differently depending on the stage of the cell cycle.
In eukaryotes, like ourselves, our
DNA is located inside the nucleus of our cells. There’s actually a lot of DNA
compacted into such a tiny place. If we were to take out the DNA from
the nucleus of one of our body cells and uncompact it and stretch it out, we would
have about two meters worth of DNA. That’s about the size of our human
here, and it’s about 20,000 times larger than the size of an average human cell. So how does all this DNA even fit
inside the nucleus of a cell? The DNA is compacted, a lot. But before we get into that, let’s
first talk about how this DNA is organized in our cells.
In humans, we don’t have one long
molecule of DNA but rather 46 smaller molecules of DNA that we call chromosomes. A chromosome is a long molecule of
DNA and its associated proteins. We’ll learn more about these
proteins in a little bit. But first, let’s look at what our
46 chromosomes look like. They’re numbered from one to 22
based on their size, where chromosome one is larger than chromosome 22. The sex chromosomes X and Y are
what determine our biological sex. We have two copies of each
chromosome. One is represented in blue that we
get from our biological father, and one is represented in pink that we get from our
biological mother. If we were to take all these
chromosomes and line them up and accounting for the pink chromosomes also, this is
how we would get about the two meters of DNA that we see here.
Now, before we talk about how we
can package two meters of DNA so it fits inside the nucleus, let’s spend a bit of
time talking about how the word chromosome can mean slightly different things. When we look at the nucleus of a
cell with a microscope, we can see the DNA as either a messy bundle or as these
individual X-shaped structures. Both of these nuclei have
chromosomes, but they’re packaged a bit differently. And this depends on what stage of
the cell cycle they’re in. You recall that the cell cycle is a
series of steps a cell takes in order to divide.
During interphase, the cell’s DNA
is copied, while during mitosis, the cell begins to separate this copied DNA in
several steps while prepares to divide to form another cell. At the end of mitosis, the cell
divides. If the cell is in interphase or if
it isn’t even in the cell cycle, then these chromosomes will exist mainly as long
fibers of DNA that are all mixed up as we could see here. If we zoom in to a section of the
nucleus, we can see that each chromosome is represented by a different color. So this orange fiber could be
chromosome one, and this red one could be chromosome 22. These are very long fibers, so they
wind around each other many times. So it’s not possible to distinguish
chromosome one from chromosome 22. We call this state chromatin.
These chromosomes in chromatin are
compacted forms of DNA and are not simply DNA molecules, but we’ll talk about that
in a moment. Chromatin is fine for the
undividing cell. But during mitosis, these
chromosomes need to be separated for cell division. Chromatin is a bit unorganized, so
the cell compacts these chromatin fibers further to form what’s called a condensed
chromosome. These condensed chromosomes are the
structures you probably recognize as chromosomes. So let’s take a closer look.
This is a condensed chromosome,
where the chromatin fibers are wound up very tightly to form this structure. This is actually a duplicated
chromosome and is what we get after the DNA is copied during the cell cycle. The single chromosome is doubled to
make two. These can then be separated during
mitosis to split these copies between the cells. So during mitosis is when we can
actually make out these individual chromosomes under the microscope. So the word chromosome is actually
a bit tricky because they can refer to the single long molecule of DNA that we saw
in here. Or it can refer to this condensed
duplicated structure that we see here. Now that we understand a bit more
about what chromosomes are, let’s start from the beginning and see how a free
molecule of DNA can be compacted to form a condensed chromosome structure.
In order to fit two meters of DNA
into a tiny nucleus, it needs to go through several levels of compaction. The first step is that the DNA is
coiled around specialized proteins called histones. Histones are proteins that are able
to interact with DNA very closely. This happens because histones
contain many positively charged amino acids like arginine and lysine, while DNA
carries a negative charge due to the phosphate group in its sugar phosphate
backbone. So the positively charged histones
can interact closely with a negatively charged DNA. This allows DNA to coil around
groups of histone proteins, and this structure is called a nucleosome. Although it looks like there’s only
four histone proteins here, there’s actually eight and about 146 nucleotides of DNA
that’s wrapped around them to form the nucleosome.
As we’ll see, a nucleosome is
actually a subunit of chromatin, the level of compaction of DNA that we had seen
earlier, which contains compacted DNA wrapped around histone proteins. So DNA continues to be compacted
into nucleosomes. And then these nucleosomes begin to
coil up themselves. These nucleosomes continue to coil
up to form long fibers. These fibers are called
chromatin. And this is the state of DNA in the
nondividing cell that we had seen earlier. When we break it down, chromatin is
really just a complex of DNA and protein that represents a level of compaction of
DNA where the nucleosome is a subunit.
Chromatin is the level of
compaction for many cells. But for the cells that are
preparing to divide, they need to compact this chromatin further to form the
condensed chromosome structure. And at this point, we’re able to
make out the individual chromosomes under the microscope. Now, let’s talk a little bit about
the different types of chromatin and how it can be remodeled to regulate gene
expression. Besides acting as a form of DNA
compaction, chromatin can also be used to regulate how genes are expressed. There’re basically two forms of
chromatin. Euchromatin is loose and open,
while heterochromatin is compacted and closed. Let’s imagine that there were two
very tiny genes in this diagram, gene A and gene B. Gene A is located in the
euchromatin as shown in pink, and gene B is located in the heterochromatin as shown
in green.
Gene expression or transcription
involves different proteins including our tiny RNA polymerase here. These need to physically interact
with the gene in order to make an mRNA transcript. When chromatin is opened up as
euchromatin, it’s accessible to RNA polymerase and other proteins needed for
transcription. In heterochromatin, the DNA is not
accessible, so RNA polymerase and other proteins would not be able to perform
transcription. So in this case, gene A would be
transcribed and gene B wouldn’t. These states of chromatin can be
changed or remodeled by the cell in order to control the expression of genes. So in this way, genes that need to
be expressed frequently would be in the euchromatin state, while genes that need to
be turned off or downregulated can be in the heterochromatin state.
This can be the difference between
one cell type and another. When you were just an embryo, these
embryonic cells, called embryonic stem cells, had the potential to turn into the
hundreds of different cell types inside your body. These stem cells may actually have
higher amounts of euchromatin. In fact, when you look at one of
these cells under the microscope, they have large nuclei. This might be due to the abundance
of loose euchromatin. In contrast, when these cells
change or differentiate into more specialized cells, like an immune cell, for
example, some of these regions of euchromatin can compact into the more dense
heterochromatin, and the nucleus can appear smaller.
By converting the euchromatin to
heterochromatin, many genes that are needed by the immune cell can become
inaccessible and can’t be expressed, while genes that are needed will remain open to
transcription on the euchromatin. So in this way, chromatin can be
remodeled so only certain genes are expressed. This can create gene expression
programs and is how a skin cell can be a skin cell and not a liver cell, for
instance. Now that we’ve covered DNA in
eukaryotes, let’s try at a practice question.
DNA is wrapped around proteins and
coiled into loops to form chromatin. At what point will chromatin
condense to form visible chromosomes? (A) When cells are stimulated by
chemical messengers. (B) When cells become
fertilized. (C) As cells prepare for cell
division. (D) Shortly after cells have
completed cell division. Or (E) immediately after chromatin
has formed.
This question is asking us about
how DNA can be compacted in eukaryotes to form chromatin which can then be compacted
further, or condensed, to form visible chromosomes. Let’s first start by looking at
what chromosomes are and how they’re compacted.
In humans, our DNA can be found in
the nucleus of most cells. If you were to take the DNA out of
one of our cells and line it end to end, it would be about two meters in length. This is not one long continuous
piece of DNA. Instead, DNA is organized into 46
chromosomes in most of our cells. Each chromosome is a linear piece
of DNA, and if they’re lined up together, then it’s about two meters in length. To squeeze this amount of DNA into
a tiny cell requires a lot of compaction. Let’s look at how DNA can be
compacted to this degree.
DNA is first wrapped around special
proteins called histones to form a structure called a nucleosome. These nucleosomes are then coiled
around and around to form long dense fibers called chromatin. Chromatin can then be wrapped up
even more to form what’s called a condensed chromosome. This condensed chromosome is the
structure you may be most familiar with when talking about chromosomes. Before this, chromosomes exist
mainly as very long strings of somewhat loose chromatin. We can actually find these two
states of compacted DNA in our cells. On the bottom, the cell on the left
has its chromosomes in the condensed arrangement, while the cell on the right has it
in the chromatin arrangement. What determines whether or not the
DNA is in the chromatin or the condensed chromosome state has to do with what part
of the cell cycle the cell is in.
You recall that the cell cycle is a
cycle that cells go through as they divide. Interphase is a long stage where
DNA is copied, and mitosis is made up of several steps where this copied DNA is
separated into a new dividing cell. Chromatin is a state that DNA is in
during interphase as the DNA is being copied. Each chromosome, and there’s 46 of
them in human cells, is hard to make out because they’re long and all mixed up with
each other. This is what it might look like if
there were three chromosomes, each color blue, green, or orange in the chromatin
state.
If we stretched out one of these
chromosomes, the orange one, for example, it might look like this. Then, during interphase, it’s
copied. Then, it’s wrapped up and compacted
in preparation for mitosis and cell division to eventually give rise to the
condensed chromosome that’s visible under the light microscope. This familiar X-shaped chromosome
actually contains two separate copies of the chromosome. And these can be separated as the
cell divides. Therefore, chromatin compacts or
condenses to form visible chromosomes as the cell prepares for cell division.
Now let’s take a moment to go over
some of the key points that we covered in this video. DNA in eukaryotes can be wrapped
around histone proteins to form nucleosomes. These nucleosomes can then be
coiled to form long fibers called chromatin. Chromatin can then be compacted
further, or condensed, to form a condensed chromosome structure. This represents a highly compacted
form of DNA. Chromosomes can exist as long
chromatin fibers or as condensed chromosomes as the cell prepares to divide.
