The Biosphere

WYSIWYG

09:31

@KoustavPal there?

Koustav Pal

yup

WYSIWYG

@KoustavPal I was saying that the definition of epigenetics has loopholes in many places.

If it is a concept of non-genetic heritability then it should have other concepts within its domain and it should exclude topics like chromatin dynamics and miRNAs

If you go by rg255's point of view then all modes of gene regulation should be considered epigenetic.

On self sustaining systems: if a system has multiple stable states (lets for simplicity consider just two), then depending on its initial condition the cell would go to one of the states.

If a replicating cell just provides those initial conditions for the new cell, it will sustain the state. Now, the cell can also provide different initial conditions to its different progeny which leads to asymmetric division.

You can see these mechanisms in eukaryotic cells but they have also become dependent on histone modifications etc. Therefore it would not be easy to experimentally demonstrate an endogenous heritable system in absence of these mechanisms. It should be possible, though. You can always create a synthetic network which does not affect the cell's survivability.

Koustav Pal

09:58

First, I'll just say the concrete definition of epigenetics is still evolving similar to the definition of gene, which has seen some change in the last few years.

Having said so, yes epigenetics has come to encompass a a very broad set of fields which have some sort of effect on heritability, but what it does not include is heritable genetic changes.

as you rightly point out chromatin dynamics should not be in this super set. That is a point of contention in the field, did conservative heritable genetic changes (histone modification, methylation) come first or did chromatin dynamics come first. Some would say, the former affected the latter, I being biased would say the latter also affects the former, citing this publication nature.com/doifinder/10.1038/nature18589. Therefore, epigenetics should encompass chromatin dynamics

*it does not include heritable genetic mutations. Typo error

WYSIWYG

@KoustavPal Epigenetics should also encompass every other mechanism that leads to non-genetic heritable change. The focus should be on the heritability.

Koustav Pal

Finally, I do accept the premise that a system with multiple stable states, will lead to different progenies all perpetuating a different stable state. That has been shown and proven by the multitude of single cell expression analysis publications

WYSIWYG

But then you have many genes that would regulate HDAC lets say. Would you count them in epigentics? Ideally, you should.

@FoldedChromatin So you officially changed your name to endorse your point of view eh? :P

FoldedChromatin

Yes!

WYSIWYG

10:13

Yes for what - the first statement or the second?

FoldedChromatin

Second

Your question to the first was if a gene affects an HDAC depositions, should it not be counted as a epigenetic mechanism

WYSIWYG

Yes. That is just an example. There are multiples examples like this.

FoldedChromatin

I would say, that we should not count genes but rather the skeletal framework within which it affects HDAC depositions as an epigenetic mechanism

WYSIWYG

Why not? If it should not be then why consider chromatin folding etc? That is also either a consequence or, as you said, a potential cause of histone modification.

FoldedChromatin

Which for me would be to somehow affect cohesin or CTCF or other archtectural proteins which all fall within the broader bounds of chromatin architecture.

WYSIWYG

10:20

So there is some gene that represses CTCF. Would that be a part of epigenetics? Also, anaphase promoting complex affects cohesin. Would you consider that epigenetic?

FoldedChromatin

As I said, I would not consider the gene as epigenetic, because epigenetics does not encompass genes per se, but rather broad functional frameworks, here the functional context comes into play. Does, the functioning of anaphase promoting complex somehow lead to perpetuating heritable change? No. It does not, it affects separation of sister chromatids, this should not be an epigenetic change.

I am currently exploring the possibility of non-coding RNA expression near CTCF binding sites which affects CTCF binding on the genome.

This particular expression will continuously perpetuate across generations being inherited by the progenies of the cell

I would say then that this expression of a non-coding RNA is falling within the broader bounds of chromatin architecture which is heritable (this statement makes me a lynching candidate in some places).

WYSIWYG

11:00

> because epigenetics does not encompass genes per se

...

why not?

@FoldedChromatin It is fine if you are applying to a funding agency/conference dedicated to epigenetics :P But if ncRNA can be included then so can be proteins.

terdon

@FoldedChromatin Surely you'd say that only if the expression is being regulated through epigenetic mechanisms. Or, rather, that the expression level is inheritable because of epigenetic mechanisms. Otherwise, why would you consider an NC RNA as falling under epigenetics?

FoldedChromatin

@WYSIWYG I never said the ncRNA should be..but the mechanism itself if it alters the CTCF binding potentially leading to different architectural features, which in turn would lead to an altered transcriptional output > altered protein profile, then it is epigenetic.

terdon

Or, to take a more extreme example. Imagine a cell with a specific salinity in its cytoplasm. This salinity would be inherited by the daughter cells and could, conceivably, affect some cellular functions. Let's, for the sake of argument, imagine a gene whose expression level is controlled by the salinity of the cytoplasm.

In such cases, and assuming there is no other mechanism that would change the salinity, you'd have an inheritable change that has nothing to do with either genes or even DNA in general.

You wouldn't call this fictitious scenario an epigenetic issue would you?

WYSIWYG

@FoldedChromatin Similarly, if a protein (transcription factor) affects CTCF concentrations, it would ultimately lead to the same kind of outcomes (change in methylation state > altered transcriptional output > altered protein profile).

FoldedChromatin

@WYSIWYG if it affects the binding leading to the same, the function would for me come under the broader realms of epigenetics.

but not the protein itself

Jeff Teoh

11:15

Hey

WYSIWYG

@FoldedChromatin Well, not the binding; just the expression. Nevertheless, why should CTCF be an epigenetic protein and the one that regulates it, not one.

Hello @JeffTeoh

Jeff Teoh

IS this chat about biology?

WYSIWYG

Yes of course. We are debating on what constitutes epigenetics.

FoldedChromatin

@terdon if such a simple mechanism existed...are you by any chance making a reference to the Riken incident? If changing the salinity of the cytoplasm then changes the expression of the genome, it will be heritable and the daughter cell would produce an altered profile. I would consider that as an epigenetic mechanism.

Jeff Teoh

I see, haha. I have never heard about that. I'm still in year 10.. haha

WYSIWYG

11:18

@FoldedChromatin Such mechanisms exist a lot. As I said, the state can be inherited just because of the initial conditions of the daughter cell.

Jeff Teoh

Interesting. Currently studying about genetics.

I'll leave you guys to it.

FoldedChromatin

@WYSIWYG I do not say that CTCF is an epigenetic protein, it's an architectural protein among other things. But CTCF demarcates domain boundaries and affects transcriptional regulation and co expression of genes, these regions also define how long range chromatin interactions happen. These are all functions which are affected by chromatin architecture/genome conformation/genome folding. Therefore chromatin architecture falls within epigenetics

Jeff Teoh

Don't mean to disrupt your debate. However, is Genotype what we can see in an organism?

WYSIWYG

@FoldedChromatin You are saying that long range chromatin changes are associated with epigenetic inheritance. Yes, there are some cases like that. However, change of chromatin state does not necessarily cause an epigenetic inheritance and neither does an epigenetic inheritance necessitate chromatin reorganization.

terdon

@FoldedChromatin No, just made something up to have a simple example. I see no reason to call something epigenetic if it doesn't actively involve DNA. After all, epigenetic just means "non-sequence based inheritable changes to the genome". What I described is inheritable through mechanisms that have nothing to do with the genome so shouldn't be epigenetics.

@JeffTeoh Genotype is what the organism has. Phenotype is the visible (or not) effect of the genotype. So, your genotype would be which versions of a gene you have and the phenotype would be that your hair is blonde or whatever.

Jeff Teoh

11:26

@terdon Ah, thanks.

terdon

np

WYSIWYG

@JeffTeoh However, now we have the technology to see the genotype as well :)

Jeff Teoh

yup!

FoldedChromatin

I am never going to say that CTCF is an epigenetic protein. I do not believe such a thing even exists, Epigenetics is at least for me a broad term describing a complex set of functional hierarchies which can all facilitate an altered transcriptional output which is inherited

terdon

@FoldedChromatin All of which need to be somehow related to DNA though, right? For me, epigenetics describes all inheritable changes to DNA that don't actually change the sequence. If there's no DNA involved, it ain't epigenetics.

FoldedChromatin

11:30

@terdon Exactly, somehow they have to involve DNA. If these mechanisms do then yes they are falling within that super set.

WYSIWYG

@terdon But isn't everything that is endogenous, somehow involve the DNA?

Like in your case, the "inheritance" is because of sustained exogenous stimulus.

So that would not be epigenetic. However, what would you consider the process of mitochondria being inherited?

In most cases mitochondrial segregation is controlled by nuclear genes. So, DNA is involved.

FoldedChromatin

@WYSIWYG There are multiple studies which have tried to show that chromatin architecture is different between different lineages (it isn't) all have failed, because broadly speaking large architectural features don't change. But there is evidence for changes in local architectural features, and these are different between different lineages.

WYSIWYG

@FoldedChromatin Yes. But it depends on what would you consider an architecture. In a gross scale the structural features would not change. However, when you zoom in, you'll see difference in nucleosome positions etc.

FoldedChromatin

@WYSIWYG When I say large features I mean on a scale of 25 kilobase genomic regions. Ofcourse we will not see changes there, but there are studies which show differences in fragment level with an average restriction fragment size range of 1.2kb - 4kb.

terdon

@WYSIWYG Well, if I were to call something epigenetic, its mechanism would have to involve some kind of DNA modification. And I count histones etc as part of DNA for this definition. So, let's say some kind of chromosomal modification.

WYSIWYG

11:38

@FoldedChromatin yeah even the DHS changes.

@terdon If you restrict to chromosomal modification, then the all inclusive definition of non-genetic inheritance is dissolved.

We can restrict the definition to that but it should be consistent.

Plus, all chromosomal modifications need not cause inheritance of the state.

terdon

@WYSIWYG Indeed. If we call something foogenetic it must somehow involve DNA.

WYSIWYG

@terdon ah ha. However, epigenetic clearly means other than genetic.

Jeff Teoh

Is Karyotype an image of the DNA found in all our cells?

FoldedChromatin

@JeffTeoh Is that your homework?

terdon

@WYSIWYG No, it means on top of genetic.

Karyotype

A karyotype (from Greek κάρυον karyon, "kernel", "seed", or "nucleus", and τύπος typos, "general form") is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism. Karyotypes describe the chromosome count of an organism and what these chromosomes look like under a light microscope. Attention is paid to their length, the position of the centromeres, banding pattern, any differences between the sex chromosomes, and any other physical characteristics. The preparation and study of...

Jeff Teoh

11:50

Well, my teacher instructed us to find definitions. I came upon Karyotype, and one user asked about whether karyotype an image of the DNA found in all our cells

WYSIWYG

@terdon well yes but doesn't that refer to mechanisms that are additional to genetic mechanisms?

Jeff Teoh

So kinda out of curiosity. As no one really answered him.

terdon

@WYSIWYG For me, it refers to mechanisms that aren't the classical sequence based ones. changes that affect the molecule/chromosome without changing the sequence.

FoldedChromatin

@WYSIWYG I would say epigenetic mechanisms alter DNA functionality without changing sequence

terdon

^^

Jeff Teoh

11:51

But I think I got it.

WYSIWYG

@FoldedChromatin yes indeed but that need not require chromosome modifications. Anyway, one thing is quite clear - ncRNAs would not constitute epigenetics unless they cause DNA modifications.

arboviral

14:55

Gah - just found an interesting paper and added it to biology.stackexchange.com/questions/48269/… but I forgot this had been closed. Any suggestions on how to rewrite it to get it reopened? I still don't really agree with 'opinion-based' (as I noted in the comments) and I don't think it's too broad since it's 'Do any...' (so the answer is unequivocally 'yes').

terdon

16:24

@arboviral Well, the classic approach is to post on meta explaining your reasons for wanting it reopened.

That said, it does seem kinda too broad. Are there any prey animals that haven't evolved stealth? The OP seems to think that because he can sometimes hear squirrels, they never move silently.

CowperKettle

18:37

How does one call it when a worker after\before working in a clean room undergoes testing for microorganisms: his forearm is swabbed and the swab's CFU count is assessed?

rg255

19:06

I see no reason why my answer was downvoted - mimat claims it's wrong but I didn't make a claim that miRNA was epigenetic, I just explained what epigenetic effects were. Since then I have edited to add detail on the problems of defining miRNA effects as epigenetic... Anyone got any hints?

3

Q: Is post-transcriptional regulation of gene expression an epigenetic process?

Is post-transcriptional regulation of gene expression (for example regulation by microRNAs) a type of epigenetic gene expression regulation? I think we can categorize it as epigenetic since the DNA sequence is not changed, but I have never come across that terming in any papers. Does someone ha...

arboviral

22:33

@terdon Well, you could claim that you think that's happened, but actually the question made me realise that I couldn't think of any studies that actually did a proper study of this, at least initially. If you can point me at ten I'd happily accept the closure, but on reflection I thought it was actually a surprisingly good question. Personally, I suspect most prey using crypsis just go for visual; once you've been seen it doesn't matter how quiet you are, you're dinner.

(and conversely crickets and grasshoppers demonstrate quite well that with good visual crypsis you can make a hell of a racket and still be bloody difficult to find).

MattDMo

23:03

@rg255 it looks like someone went on a down-voting spree on that question. Strange...

@CowperKettle Environmental monitoring?

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