Sperm.
We all know what sperm is, right? And we know what happens when it fuses with the egg cell, right? Well, partly. You probably know all the blah about the sperm entering the egg cell, the DNA fusing and the cell then divides, over and over again, until we have a human.
But that’s only part of the story.
The DNA in sperm is very, very compressed, so it fits all in that tiny cell. A sperm cell doesn’t contain much aside from DNA, in contrary to an egg cell. Why should it? The egg cell provides anything it needs!
But as soon as it enters the egg cell, it needs to unpack and epigenetic adjustments have to be made.
Too fast? Let’s slow down.
Epigenetics
Genetics is what’s written in our genes, what can only be changed through mutation or artificial gene editing. But you’ve probably heard about things or behaviors having “an effect on your genetics”. That’s usually tied to epigenetics (epi = over/outside of/around).
There are two (technically three but the third caused a big argument in my lab so we’ll stick with two) epigenetic mechanisms.
- DNA modification
- Histone modification
Histones are the proteins which keep DNA tightly packaged, which is necessary because our DNA is really, really long. Histone modifications interact with DNA modifications in many ways, the two influence each other. It’s pretty complicated, especially if you have no background knowledge in genetics. So we’ll focus on something simpler.
DNA methylation is a modification of the DNA where a methyl group (that’s one carbon (C) atom and three hydrogen (H) atoms) is added to a specific part of the DNA (in eukaryotic cells, it’s added to the base cytosine. For those who don’t know what that “eukaryotic” or “cytosine” means: It’s not that important for what I want to tell you).
When a part of the DNA is methylated, the gene can’t be “read” and thus no protein for it can be produced. The gene is effectively “turned off”.
DNA Methylation in Mouse sperm
What I’m currently looking into is the development of mouse embryos (short version). The interesting part in this is what happens after the sperm has entered the egg cell and before the cell divides the first time. Because more things happen than you might think!
As I said earlier, the sperm DNA (I’ll call it “paternal” DNA from now on, the egg cell DNA will be the “maternal” DNA) is very tightly packed. But not just that! It has a very high amount of methylated Genes.
During the first few hours after fertilization, paternal and maternal DNA seem to “increase in size”, which is mostly due to the fact that they’re being “unpacked” (like a zip file!). The paternal DNA seems to increase a lot more, for some currently unknown reason.
And something else happens.
While the amount of methylated genes in the maternal DNA stays roughly the same, the methylation of paternal genes … decreases! A lot!
Active and Passive Demethylation
There are several reasons why methylation can be lost.
When DNA is replicated, it happens semi-conservative. That means the double strand is separated and each half serves as a template for the new double strand. If only one of them carries the methylation, only one of the new strands will have that too. The effect is basically a “dilution” and called “passive demethylation”.
That one can’t be the reason tho, as the demethylation happens before the cell divides and before the DNA is replicated.
Active demethylation requires, as the name indicates, an active removal of the methyl group. But that requires energy, a lot of energy. And specialized enzymes. And the demethylation doesn’t exactly happen without any side effects, no. The process causes significant damage to the DNA, which has to be repaired.
There have been experiments that have shown that active demethylation really happens, which means the paternal DNA is repeatedly cut and repaired. But it still doesn’t account for the sheer mass of changes.
The Joys of Oxidation
Wikipedia defines oxidation as
a chemical reaction in which the oxidation states of atoms are changed.
That’s a super useless explanation for everyone who didn’t take chemistry in high school or college/university. What oxidation often means in biology is
we just added an oxygen atom.
That’s a bit easier to understand, isn’t it? And of course, that’s technically what happens to the methyl groups.
Through the influence of a certain enzyme, this
Turns into this
Which can be oxidized again … and again. You get the gist. Important thing is, this oxidation is enough to make the methyl group seem to “disappear” when you measure it with the help of fluorescent antibodies (what’s that? Something cool I might explain another time).
Now, the question is: Why does this happen only to the paternal DNA, not the maternal? Why does it happen at all? What happens if we manage to turn it off? Or only partly off?
That’s research which is currently happening, and in which I’ll be taking part.
Closing Words
I hope you were able to understand/learn something from this post, even if it’s just “Wow, genetics and epigenetics are nuts, what the fuck” because that’s already something.
I won’t act like it’s super easy to understand, it’s a complicated subject and it was less than easy for me to break it down in under 1000 words. But it’s what I’m working on at the moment and I enjoy sharing it.
I plan on doing that more frequently from now on, break down some parts of what I’m working with (which is A LOT!).
Ask if you want to know more 😊
Sources:
5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Active demethylation in mouse zygotes involves cytosine deamination and base excision repair
Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes.
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