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Posts Tagged ‘Nessa Carey

epigenetics and imprinting 4: the male-female thing

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Gametes are gametes because of epigenetic modifications in their pro-nuclei, but they have to lose these modifications, or transform them, when they come together to form zygotes. The male pro-nucleus DNA methylation is stripped away immediately after sperm penetrates egg. The egg pronucleus undergoes the same process, but more gradually. It’s like a wiping away of epigenetic memory, creating totipotency, which becomes a more limited pluripotency as the blastocyst, with its inner cell mass (ICM), forms. 

The ICM cells begin differentiating through the regulation of some key genes. For example, a gene codes for a protein that switches on a set of genes, which code for proteins in a cascading effect. But it’s not quite a matter of switching genes on or off, it’s rather more complex. The process is called gene reprogramming, and it’s of course done effortlessly during every reproductive cycle. Artificial reprogramming of the kind carried out by Yamanaka and others, an essential part of cloning, hasn’t come close to this natural process that goes on in mammals and other species every day.

Clearly, though the epigenetic reprogramming for the female pronucleus is different from that carried out more swiftly in the male. As Carey puts it, ‘the pattern of epigenetic modifications in sperm is one that allows the male pronucleus to be reprogrammed relatively easily.’ Human researchers haven’t been particularly successful in reprogramming an adult nucleus by various methods, such as transferring it to a fertilised egg or treating it with the four genes isolated by Yamanaka. The natural process of gene reprogramming eliminates most of the epigenetic effects accumulated in the parent genes, but as the reprogramming is a different process in the male and female pro-nucleus, this shows that they aren’t functionally equivalent. There is a ‘parent-of-origin effect’. Experiments done on mice to explore this effect found that DNA methylation, an important form of chromatin modification (and the first one discovered), was passed on to offspring by the female parent. That’s to say, DNA from the female was more heavily methylated than that from the male. Carey describes the DNA as ‘bar-coded’ as coming from the male or the female. The common term for this is imprinting, and it’s entirely epigenetic.

Imprinting has been cast by Carey, and no doubt others, as an aspect of the ‘battle of the sexes’. This battle may well be imprinted in the pronuclei of the fertilised egg. Here’s how Carey puts the two opposing positions:

Male: This pregnant female is carrying my genes in the form of this foetus. I may never mate with her again. I want my foetus to get as big as possible so that it has the greatest chance of passing on my genes.

Female: I want this foetus to pass on my genes. But I don’t want it to be at the cost of draining me so much that I never reproduce again. I want more than this one chance to pass on my genes.

So there’s a kind of balance that has developed in we eutherian mammals, in a battle to ensure that neither sex gains the upper hand. Further experiments on mice in recent times have explored how this battle is played out epigenetically. I’ll look at them in the next post in this series.

Reference

The Epigenetics Revolution, by Nessa Carey, 2011

Written by stewart henderson

January 9, 2020 at 10:50 am

epigenetics and imprinting 2: identical genes and non-identical phenotypes

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I’ve now listened to a talk given by Nessa Carey (author of The epigenetic revolution) at the Royal Institution, but I don’t think she even mentioned imprinting, so I may not mention it again in this post, but I’ll get back to it. 

The talk was of course easier to follow than the book, and it didn’t really teach me anything new, but it did hammer home some points that I should’ve mentioned at the outset, and that is that it’s obvious that genetics isn’t the whole story of our inheritance and development because it doesn’t begin to explain how, from one fertilised egg – the union of, or pairing of, two sets of chromosomes – we get, via divisions upon divisions upon divisions, a complex being with brain cells, blood cells, skin cells, liver cells and so forth, all with identical DNA. It also doesn’t explain how a maggot becomes a fly with the same set of genes (or a caterpillar becomes a butterfly, to be a little more uplifting). These transformations, which maintain genetic inheritance while involving massive change, must be instigated and shaped by something over and above genetics but intimately related to it – hence epigenetics. Other examples include whether a crocodile hatchling will turn out male or female – determined epigenetically via the temperature during development, rather than genetically via the Y chromosome in mammals.   

So, to add to the description I gave last time, the histone proteins that the DNA wraps itself round come in batches or clusters of eight. The DNA wraps around one cluster, then another, and so on with millions of these histone clusters (which have much-studied ‘tails’ sticking out of them). And I should also remind myself that our DNA comes in a four-letter code strung together, out of which is constructed 3 billion or so letters.

The detailed description here is important (I hope). One gene will be wrapped around multiple histone clusters. Carey, in her talk, gave the example of a gene that breaks down alcohol faster in response to consumption over time. As Carey says, ‘[the body] has switched on higher expression of the gene that breaks down alcohol’. The response to this higher alcohol consumption is that signals are generated in the liver which induce modifications in the histone tails, which drive up gene expression. If you then reduce your alcohol consumption over time, further modifications will inhibit gene expression. And it won’t necessarily be a matter of off or on, but more like less or more, and the modifications may relate to perhaps an endless variety of other stimuli, so that it can get very complicated. We’re talking about modifications to proteins but there can also be modifications to DNA itself. These modifications are more permanent, generally. This is what creates specialised cells – it’s what prevents brain cells from creating haemoglobin, etc. Those genes are ‘tightened up’ or compacted in neurons by the modifying agents, so that, for example, they’re permanently unable to express the haemoglobin-creating function.

All of this is extremely fascinating and complex, of course, but the most fascinating – the most controversial and headline-creating stuff – has to do with carrying epigenetic changes to the next generation. The inheritance of acquired characteristics, no less. Next time.

References

What is epigenetics? with Nessa Carey – The Royal Institution (video)

The Epigenetics Revolution, by Nessa Carey, 2011

Written by stewart henderson

January 3, 2020 at 3:58 pm