Epigenetic control of regulation

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We could look at making terms for epigenetic control of gene expression.

Reported by: jenclark

Original Ticket: "geneontology/ontology-requests/809":https://sourceforge.net/p/geneontology/ontology-requests/809

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Hi Jen,

There's already:

regulation of gene expression\, epigenetic ; GO:0040029 (and its children)

(just incase you haven't seen it) Becky

Original comment by: beckyfoulger

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Gosh!

You're right. I was just writing those terms from scratch, thanks for pointing them out. I wonder why the search missed them. Have to think about that.

Midori was just saying that we shouldn't really have Polycomb-specific terms. But that the process of heritable epigenetic silencing is fine. I think it might be better if I just obsolete all those polycomb/trithorax terms and give the epigenetics terms the additional parent 'chromatin modeling'. Would that suit you?

Jen

Original comment by: jenclark

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N.B. this page is continuation of 728983

Original comment by: jenclark

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I don't know much (atall!) about epigenetic gene expression. Does it always involve chromatin remodelling?

Also, gene expression is broader than gene transcription so I'm a bit wary about giving GO:0040029 the extra parentage.

How about making a new term as a child of both that can be a direct replacement for the homeotic gene terms:

term: chromatin-induced regulation of transcription\, epigenetic parent: regulation of gene expression\, epigenetic ; GO:0040029 parent: regulation of transcription\, DNA-dependent ; GO:0006355 parent: chromatin modeling ; GO:0006338 def: Regulation of transcription by remodelling of chromatin into an 'open' or 'closed' configuration. Once established, this regulation is mitotically stable and is maintained over many cell divisions.

And then as its children:

term: chromatin-induced negative regulation of transcription\, epigenetic synonym: negative regulation of homeotic gene transcription (Polycomb group) ; GO:0006340 parent: chromatin-induced regulation of transcription\, epigenetic ; GO:new parent: negative regulation of gene expression\, epigenetic ; GO:0045814 parent: negative regulation of transcription\, DNA-dependent ; GO:0045892 parent: chromatin silencing; GO:0006342 def: Repression of transcription by remodelling of chromatin into a 'closed' configuration. Once established, this regulation is mitotically stable and is maintained over many cell divisions.

term: chromatin-induced positive regulation of transcription\, epigenetic synonym: positive regulation of homeotic gene transcription (trithorax group) ; GO:0006339 parent: chromatin-induced regulation of transcription\, epigenetic parent: positive regulation of gene expression\, epigenetic parent: positive regulation of transcription, DNA-dependent def: Activation or maintenance of transcription by remodelling of chromatin into an 'open configuration. Once established, this regulation is mitotically stable and is maintained over many cell divisions.

In terms of curation, it would be v. useful to have the homeotic process terms as synonyms, or add a bit into the def of these terms:

This regulation is exemplified by members of the trithorax group, which maintain the active state of homeotic gene transcription.

This regulation is exemplified by members of the Polycomb group, which maintain the inactive state of homeotic gene transcription.

It's a tad wordy, but what do you think?

Becky

Original comment by: beckyfoulger

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Hiya, Midori points out that the best place for this:

In terms of curation, it would be v. useful to have the homeotic process terms as synonyms, or add a bit into the def of these terms:

This regulation is exemplified by members of the trithorax group, which maintain the active state of homeotic gene transcription.

This regulation is exemplified by members of the Polycomb group, which maintain the inactive state of homeotic gene transcription.

...would be the comments field. Would that work for you?

Jen

Original comment by: jenclark

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Midori points out that the best place for this: ...would be the comments field. Would that work for you?

yep - fine by me!

Original comment by: beckyfoulger

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I was just looking through what you suggested for the polycomb gene stuff and I think it's really good. :-)

One think that I wondered is that there's a term:

chromatin silencing; GO:0006342

and it seems as though there ought to be an equivalent term that covers the trithorax version where the gene is stuck activated rather than stuck silenced.

I was thinking about adding something like

persistent chromatin-mediated activation of transcription ; GO:new def: Maintenance of transcription by conversion of large regions of DNA into an accessible state by heterochromatin modelling.

Original comment by: jenclark

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Ok- I admit I was a little lazy by not requesting such a term to start with !

I agree that it's a good idea to have this new term! There's lots of children of chromatin silencing ; GO:0006342 including maintenance of c'tin silencing ; GO:0006344. So maybe the def of the new term should be a little broader so equivalent new child terms can be added later if/when required: eg

chromatin activation ; GO:new def: Induction or maintenance of transcription by conversion of large regions of DNA into an accessible state by heterochromatin modelling. ref: Chromatin silencing and activation by Polycomb and trithorax group proteins. Oncogene. 2001 May 28;20(24):3055-66. Review. PMID: 11420721

What do you think?

Original comment by: beckyfoulger

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Yes I know what you mean :-)

Not sure about the term name yet though. I thought the chromatin was not responsible for the activation. Doesn't it just lock the gene into activated state?

How about:

maintenance of transcriptional activation, chromatin-mediated.

Original comment by: jenclark

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> Doesn't it just lock the gene into an activated state? Ah- I guess my original definitions need tweaking then!

> Not sure about the term name yet though. I know- just being lazy again and stealing it from the papers I found :)

It's a shame there's no nice simple word meaning the opposite of chromatin silencing. I think possibly 'maintenance of transcriptional activation, chromatin-mediated' sounds a little like the new trithorax child term.

Chromatin is either in a repressed or an active state. So c'tin activation in the papers I read refers to the conversion of c'tin into the open state, thus alllowing transcription to carry on (rather than activation of transcription itself).

Tho if you're still not convinced, 'maintenance of transcription, chromatin-mediated' is fine by me :)

maintenance of transcriptional activation, chromatin-mediated.

Original comment by: beckyfoulger

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Oh dear. Yes I see what you mean.

I see that gene silencing ; GO:0016458 doesn't actually have a definition at all, but that it's children include any kind of semi-permenant process that stops transcription.

The only online definition for gene silencing I find online is:

Gene silencing: A mechanism by which cells shut down large sections of chromosomal DNA. Gene silencing is done by incorporating the DNA to be silenced into a form of DNA called heterochromatin that is already silent.

which suggests that that term name should be moved to be a synonym of

chromatin-mediated negative regulation of transcription \, epigenetic parent ; GO:new

This would mean that we wouldn't need a corresponding term for activation other than the one we have already made up.

The GO:ID currently being used for gene silencing could be renamed something like:

semi-permanant repression of transcription ; GO:0016458 def: Any process that causes repression of transcription, lasting for the life of the cell, and being past on to daughter cells and possibly also to progeny.

This would take care of all the current children of gene silencing and would allow for creation of a corresponding term:

Semi-permanent maintenance of transcription. ; GO:new

Would that work for you? I can write it out long-hand if it is better.

Jen

Original comment by: jenclark

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Hi Jen,

Gene silencing is a high level GO term used to group transcriptional and post-transcriptional silencing, so it shoudln't be given that synonym and I think is ok as it is.

The original PcG terms involve chromatin silencing. I think the main Q is whether chromatin silencing/activation is always a type of epigenetic regulation.

if yes then we could:

1. Create a new term: chromatin activation (or equivalent)
2. Copy this new term AND c'tin silencing ; GO:0006342 as children of 'regulation of gene expression\, epigenetic'.

In this case: we don't need the new terms I suggested and can just obsolete the exisiting PcG and trxG terms.

If no, then we could:

1. Create a new term: chromatin activation (or equivalent)
2. Create the new terms suggested (to replace the PcG and trxG terms)

chromatin-induced regulation of transcription\, epigenetic chromatin-induced positive regulation of transcription\, epigenetic chromatin-induced negative regulation of transcription\, epigenetic

It's probably worth emailing round the group about whether c'tin silencing is epigenetic, especially since I don't want to mis-use the term. I think the epigenetic terms are fairly recent editions- since only post-transcriptional gene silencing is a current child of GO:0040029, someone may already have considered whether c'tin silencing is epigenetic and discarded this parentage (so I don't want to undo someone elses work either).

What do you think?

Becky

Original comment by: beckyfoulger

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E-mailing efforts bring the result that chromatin mediated silencing is always epigenetic so I have revised the plan accordingly.

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New terms:

Instead of having separate terms for polycomb etc. we will use the following terms and add comments to remind annotators that they are good places to put polycomb and trithorax genes.

1) Corresponding to opposite of chromatin silencing:

%long-term chromatin-mediated maintenance of transcriptional activation ; GO:new

def: Activation or maintenance of transcription by remodelling of chromatin into an 'open configuration. Once established, this regulation is mitotically stable and is maintained over many cell divisions. It is also heritable.

%chromatin modeling ; GO:006338 --%chromatin silencing ; GO:0006342 --%long-term chromatin-mediated maintenance of transcriptional activation ; GO:new

Additional parents: positive regulation of gene expression\, epigenetic ; GO:0045815 positive regulation of transcription, DNA-dependent ; GO:0045893

Add comments: ... This regulation is exemplified by members of the trithorax group, which maintain the active state of homeotic gene transcription.

---

%chromatin silencing ; GO:0006342 add synonym: long-term chromatin-mediated maintenance of transcriptional inactivation

Change term name to 'chromatin-mediated silencing'

Additional parents: negative regulation of gene expression\, epigenetic ; GO:0045814 negative regulation of transcription, DNA-dependent ; GO:0045892

Add comments: ... This regulation is exemplified by members of the Polycomb group, which maintain the inactive state of homeotic gene transcription.

Obsolete terms:

%regulation of transcription of homeotic gene (Polycomb group) ; GO:00458888 --%negative regulation of transcription of homeotic gene (Polycomb group) ; GO:0006340 --%positive regulation of transcription of homeotic gene (Polycomb group) ; GO:0045889 %regulation of transcription of homeotic gene (trithorax group) ; GO:0045890 --%negative regulation of transcription of homeotic gene (trithorax group) ; GO:0045891 --%positive regulation of transcription of homeotic gene (trithorax group) ; GO:0006339

These will all be obsoleted with the comment:

This term was made obsolete because it relates to a specific gene family rather than a process. To update annotations, consider the biological process terms 'chromatin-mediated silencing ; GO:0006342' and long-term chromatin-mediated maintenance of transcriptional activation ; GO:new

Other stuff that would be useful to do.

Add definitions:

1) gene silencing ; GO:0016458

synonym: long-term maintenance of transcriptional inactivation def: Any mechanism, at the level of transcription or post-transcription, causing long-term gene inactivation. GO:jic

2) Chromatin modeling ; GO:0016582

def:Dynamic structural changes to eukaryotic chromatin occurring throughout the cell division cycle. These changes range from the local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation. ref: GO:jic PMID: 12697820

Add term:

1) Corresponding to opposite of gene silencing:

%nucleobase, nucleoside, nucleotide and nucleic acid metabolism ; GO:0006139 --%long-term maintenance of transcriptional activation ; GO:new Def: Any mechanism, at the level of transcription or post-transcription, maintaining gene activation in the long-term.

What do you think about this?

Jen

Original comment by: jenclark

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Hi Jen,

>long-term chromatin-mediated maintenance of transcriptional activation ; GO:new >def: Activation or maintenance of transcription by remodelling of chromatin

The GO term suggests it's maintenance of transcription but the def suggests its maintenance or activation, so these should be made more consistent I think. Also in the text string, 'long-term' is a bit vague. How about just 'chromatin-mediated maintenance of transcription' ?

>chromatin silencing ; GO:0006342 >Change term name to 'chromatin-mediated silencing'

I'd be inclined to keep the term name for GO:0006342 as it is, as it's a fairly common phrase in the general literature. Could always add 'chromatin-mediated gene silencing' as a synonym?

>long-term maintenance of transcriptional activation ; GO:new >Def: Any mechanism, at the level of transcription or post-transcription, >maintaining gene activation in the long-term.

The GO term suggests it's at the transcriptional level, whereas the definition is broader. Since it's a new term to mean the opposite of 'gene silencing', it should probably cover transcriptional and post-transcriptional regulation.

1) gene silencing ; GO:0016458 >synonym: long-term maintenance of transcriptional inactivation >def: Any mechanism, at the level of transcription or >post-transcription, causing long-term gene inactivation.

Because gene silencing covers transcriptional and post-transcriptional regulation, I think the synonym may be too specific.

Thanks, Becky

Original comment by: beckyfoulger

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Ta for the comments. :-)

>>long-term chromatin-mediated maintenance of transcriptional >>activation ; GO:new >>def: Activation or maintenance of transcription by >>remodelling of chromatin

>The GO term suggests it's maintenance of transcription but >the def suggests its maintenance or activation, so these >should be made more consistent I think. >Also in the text string, 'long-term' is a bit vague. How >about just 'chromatin-mediated maintenance of transcription' ?

Good point. How about:

chromatin-mediated maintenance of transcription ; GO:new def: maintenance of transcription by remodelling of chromatin. Comment: Opposite of chromatin silencing.

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>>chromatin silencing ; GO:0006342 >>Change term name to 'chromatin-mediated silencing'

>I'd be inclined to keep the term name for GO:0006342 as it >is, as it's a fairly common phrase in the general >literature. Could always add 'chromatin-mediated gene >silencing' as a synonym?

Yep. I can do that.

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>>long-term maintenance of transcriptional activation ; GO:new >>Def: Any mechanism, at the level of transcription or post-transcription, >>maintaining gene activation in the long-term.

>The GO term suggests it's at the transcriptional level, >whereas the definition is broader. Since it's a new term to >mean the opposite of 'gene silencing', it should probably >cover transcriptional and post-transcriptional regulation.

Yep. How about: long-term maintenance of gene activation; GO:new Def: Any mechanism, at the level of transcription or post-transcription, maintaining gene activation in the long-term. Comment: Opposite of gene silencing.

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>>1) gene silencing ; GO:0016458 >>synonym: long-term maintenance of transcriptional inactivation >>def: Any mechanism, at the level of transcription or >>post-transcription, causing long-term gene inactivation.

>Because gene silencing covers transcriptional and >post-transcriptional regulation, I think the synonym may be >too specific.

True. How about: 1) gene silencing ; GO:0016458 synonym: long-term maintenance of gene inactivation def: Any mechanism, at the level of transcription or post-transcription, causing long-term gene inactivation.

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Shall I incorporate these changes into the plan?

Jen

Original comment by: jenclark

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>Shall I incorporate these changes into the plan?

Sounds good to me!- thanks!

Original comment by: beckyfoulger

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I think we're ready now. I'll e-mail this final plan around to check everyone's happy with it. (to be implemented Tuesday 10th June)

Jen

Changes:

1) Corresponding to opposite of chromatin silencing:

New term:

%chromatin-mediated maintenance of transcription ; GO:new

def: Maintenance of transcription by remodelling of chromatin into an 'open configuration. Once established, this regulation is mitotically stable and is maintained over many cell divisions. It is also heritable. Comment: Opposite of chromatin silencing.

%chromatin modeling ; GO:006338 %chromatin silencing ; GO:0006342 %long-term chromatin-mediated maintenance of transcriptional activation ; GO:new

Additional parents: positive regulation of gene expression\, epigenetic ; GO:0045815 positive regulation of transcription, DNA-dependent ; GO:0045893

Add comments: ... This regulation is exemplified by members of the trithorax group, which maintain the active state of homeotic gene transcription.

---

2) Add synonyms:

%chromatin silencing ; GO:0006342 add synonym: chromatin-mediated maintenance of transcriptional inactivation add synonym: chromatin-mediated silencing

Additional parents: negative regulation of gene expression\, epigenetic ; GO:0045814 negative regulation of transcription, DNA-dependent ; GO:0045892

Add comments: ... This regulation is exemplified by members of the Polycomb group, which maintain the inactive state of homeotic gene transcription.

3) Obsolete terms:

%regulation of transcription of homeotic gene (Polycomb group) ; GO:00458888 %negative regulation of transcription of homeotic gene (Polycomb group) ; GO:0006340 %positive regulation of transcription of homeotic gene (Polycomb group) ; GO:0045889 %regulation of transcription of homeotic gene (trithorax group) ; GO:0045890 %negative regulation of transcription of homeotic gene (trithorax group) ; GO:0045891 %positive regulation of transcription of homeotic gene (trithorax group) ; GO:0006339

These will all be obsoleted with the comment:

This term was made obsolete because it relates to a specific gene family rather than a process. To update annotations, consider the biological process terms 'chromatin silencing ; GO:0006342' and chromatin-mediated maintenance of transcription ; GO:new'.

4) Add definitions for terms that already exist:

a) gene silencing ; GO:0016458

synonym: long-term maintenance of gene inactivation def: Any mechanism, at the level of transcription or post-transcription, causing long-term gene inactivation.

b) Chromatin modeling ; GO:0016582

def:Dynamic structural changes to eukaryotic chromatin occurring throughout the cell division cycle. These changes range from the local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation. ref: GO:jic PMID: 12697820

5) Add term:

a) Corresponding to opposite of gene silencing:

%nucleobase, nucleoside, nucleotide and nucleic acid metabolism ; GO:0006139 %long-term maintenance of gene activation ; GO:new Def: Any mechanism, at the level of transcription or post-transcription, maintaining gene activation in the long-term. Comment: Opposite of gene silencing.

Original comment by: jenclark

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Shall I get on and do this one then?

Jen

Original comment by: jenclark

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New Terms added:

chromatin-mediated maintenance of transcription ; GO:0048096 long-term maintenance of gene activation ; GO:0048097

All changes made according to the list proposed in the followups below.

Original comment by: jenclark

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• status: open --> closed-fixed

Original comment by: jenclark