DNA in zygotes and somatic cells

[MarkDv]

Hi, all!

I'm looking for information if the DNA in zygotes or in blastomeres of an organism are equal to DNA in somatic cells at later stages of the organism development.

My understanding is that during the ontogenesis of organisms their DNA in specialized somatic cells are subject to more or less significant changes.However I could not find any info about it.

I would appreciate any suggestions.

Thanks!

[MarkDv]

I'm surprised that I didn't get any replies. It doesn't seem to me that the question is too complicated or very specific.

Or,  in opposite, it is very stupid?

Any suggestion why there is no replies?

Thanks!

[CharonY]

I think mostly because it is really vague and unclear in which direction you are going with this. One possible way to interpret is that there are differential epigenetic changes (such as DNA modifications) that happen at different rates and in different patterns depending on the cell line. And there are also different chromosomal re-arrangements (structurally and otherwise) depending on cell line, differentiation and so on. There is of course also the interaction of the nucleus with different signaling molecules affecting gene expression and so on. 

Or you might refer to the specific mechanisms when the haploid genomes fuse in the zygote, which is more of a developmental question. 

 

I should also add that we are a small community and if you have highly specific and/or niche questions, there is a good chances that we do not have anyone with that specific expertise able to answer questions off the top of their head.

[MarkDv]

1 hour ago, CharonY said:

I think mostly because it is really vague and unclear in which direction you are going with this. One possible way to interpret is that there are differential epigenetic changes (such as DNA modifications) that happen at different rates and in different patterns depending on the cell line. And there are also different chromosomal re-arrangements (structurally and otherwise) depending on cell line, differentiation and so on. There is of course also the interaction of the nucleus with different signaling molecules affecting gene expression and so on. 

Right. This is what I expected to hear. But I also would like to see some data on this. With the modern sequencing techniques I expected to find a lot of info about comparing initial DNA of an organism and DNA of specialized cells at later stages of development.

My question is related to understanding how the gene expression and gene silencing occurs at DNA level. Is it occurred through the structural modification of DNA or it happens due to just functional differentiation? I think this is a valid question...

I would be really surprised if nobody else would be confounded by this question. 

[CharonY]

2 hours ago, MarkDv said:

My question is related to understanding how the gene expression and gene silencing occurs at DNA level. Is it occurred through the structural modification of DNA or it happens due to just functional differentiation? I think this is a valid question...

I am not sure what you mean in terms of structural modification. Do you mean chromosomal structure and dynamics? That part is a whole research direction, but the challenge there of course is that it is not amenable to many analytical techniques. The reason being that if you isolate the chromosome to actually look at it, you are disrupting its native configuration. And observing the dynamics as well as its consequences in vivo is extremely challenging to say the least. However, there are studies on it, mostly by using clever experiments to disrupt or change chromsomal tertiary structure (e.g. by deleting or modifying proteins involved in it) but obviously that is not something that could be solved by sequencing. Likewise looking DNA methylation pattern is possible, but again, it is not done by simple sequencing, and looking their impact on gene expression requires yet another technique (say, transcriptomic measurements). Even then the translation into cell physiological impact is difficult and you also have to consider that an adult organism has many, many different cell types each with different methylation patterns and each with different consequences.

There is a considerable amount of data out there looking into many aspects ranging from developmental biology stress responses. An open question such as this cannot be easily answered as there are so many sub-specializations. To given an idea you could start looking in one older study who has basically started to make maps of cells during differentiation (Meissner et al., Nature 2008 454, 766-770), provided you can access via a library. If not you could look up open databases that have stored methylation patterns. 

While it is not my area of specialization it is my understanding that folks have gone away a bit to just do the mapping because ultimately it did not lead to massive insights. The work now tends to more targeted in order to figure out functional consequences, which takes way more time.

[MarkDv]

Thank you for your reply, Charon!

I am not sure what you mean in terms of structural modification.  

Yes, right, just after I sent my message I thought that this is quite a vague term.

I couldn't find a better way to explain... 

But yes, I'm interested to know if there is any quantitative data on how DNA changes during cell differentiation. I was certain that there should be studies on what changes DNAs undergo during cell differentiation. 
For example, if DNA modification during cell specialization is due to mostly methylation or mostly due to proteins affecting the genes? Or, perhaps, there are some changes in DNA sequencing? Or something else which I missed?

More specifically, I was wondering how gametes (which (my guess) are themselves kind of or should develop from kind of totipotent cells) are developing in mature organisms? In other words, if gametogenesis emerges from more or less specialized cells how then gametes become kind of totipotent cells even after meiosis.

 The reason being that if you isolate the chromosome to actually look at it, you are disrupting its native configuration.  

Also I do not understand why chromosomes still play such a significant role in nowadays thinking. I have an impression that DNAs organise into chromosomes only just before and during divisions while during the normal (routine) stage of the cell's life DNA looks more like tangled thread in the nucleus.

Am I missing something here?

 

[CharonY]

1 hour ago, MarkDv said:

Also I do not understand why chromosomes still play such a significant role in nowadays thinking. I have an impression that DNAs organise into chromosomes only just before and during divisions while during the normal (routine) stage of the cell's life DNA looks more like tangled thread in the nucleus.

Am I missing something here?

Yes, chromosomes are much more dynamic than initially assumed. Perhaps you are thinking exclusive about the condensed chromosomes (the typical "X" structure you see in karyotyping). However, it is actually the uncondensed chrosomes (which are more diffuse and less striking in microscopic images) when they are active (i.e. being transcribed) and how the chromosome organizes itself is dependent on many proteins (including but not exclusively by histones) controls which parts are accessible, for example.

[Dagl1]

Not entirely sure if exactly what you are asking, but potentially relevant:

DNA positioned relatively close to the nuclear lamina also undergoes inhibited gene regulation, but you could of course argue that that still is chromatin remodeling (eventually histones, cohesins, and other proteins will still be involved in the actual gene regulation). I feel lately more and more research is also looking into phase separation as an part of gene regulation, that is generally difficult to sequence as well:

Lamina-associated Domains: https://www.biorxiv.org/content/10.1101/464081v1.full 

Phase separation: https://www.cell.com/cell/fulltext/S0092-8674(18)31649-0

Edited November 28, 2020 by Dagl1

[MarkDv]

Charon and Dag,

thank you very much for your responses!

I did not get direct responses to my questions but I do realize now that it could not be. I now have a better picture of the topic I was asked about.

I need some time to take a close look at the links you provided. And think about it...

Very appreciated!