regulation of transcription by homeotic gene

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Hi,

One of our curators was annotating a paper the trithorax and Polycomb proteins in Drosophila.

These two groups of proteins (as far as I can tell) regulate transcription of the homeotic genes:

See: PMID: 11420721 Abstract: The Polycomb group (PcG) of repressors and the trithorax group (trxG) of activators maintain the correct expression of several key developmental regulators, including the homeotic genes. PcG and trxG proteins function in distinct multiprotein complexes that are believed to control transcription by changing the structure of chromatin

Therefore the following GO terms are misleading as it is the homeotic genes that are being regulated in this case. They are not doing the regulating.

regulation of transcription by homeotic gene (Polycomb group) ; GO:004588 negative regulation of transcription by homeotic gene (Polycomb group) ; GO:0006340 positive regulation of transcription by homeotic gene (Polycomb group) ; GO:0045889

regulation of transcription by homeotic gene (trithorax group) ; GO:0045890 negative regulation of transcription by homeotic gene (trithorax group) ; GO:0045891 positive regulation of transcription by homeotic gene (trithorax group) ; GO:0006339

Also, Polcomb members are transcriptional repressors and trithorax members are transcriptional activators. Therefore, the following GO terms don't apply and should be obsoleted (as far as I know this is the same in all relevant species but please correct me if I'm wrong).

positive regulation of transcription by homeotic gene (Polycomb group) ; GO:0045889 and negative regulation of transcription by homeotic gene (trithorax group) ; GO:0045891

... along with GO:0045888 and GO:0045890. According to AmiGO, there's no annotations by any groups to these 4 GO terms.

And the remaining terms and their definitions should be changed from:

negative regulation of transcription by homeotic gene (Polycomb group) ; GO:0006340 to:

term: negative regulation of homeotic gene transcription (Polycomb group) def: Any process that decreases the frequency, rate or extent of transcription from a homeotic gene, by members of the Polycomb group.

and from:

positive regulation of transcription by homeotic gene (trithorax group) ; GO:0006339

to: term: positive regulation of homeotic gene transcription (trithorax group) def: Any process that increases the frequency, rate or extent of transcription from a homeotic gene, by members of the Trithorax group.

Is this ok? thanks

Becky

Reported by: beckyfoulger

Original Ticket: "geneontology/ontology-requests/781":https://sourceforge.net/p/geneontology/ontology-requests/781

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Original comment by: girlwithglasses

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I've changed all the defs for you. I will leave the query open for other people to comment on the regulation issue before I do any obsoleting.

Original comment by: girlwithglasses

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Original comment by: girlwithglasses

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Original comment by: jenclark

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I'd like to act on this in the following way if no one has any objections: (The reasoning is explained by Beccy in the original request)

Obsolete these terms:

positive regulation of transcription by homeotic gene (Polycomb group) ; GO:0045889 and negative regulation of transcription by homeotic gene (trithorax group) ; GO:0045891

along with GO:0045888 and GO:0045890. According to AmiGO, there's no annotations by any groups to these 4 GO terms.

Make the changes to these terms that Beccy suggests:

Change negative regulation of transcription by homeotic gene (Polycomb group) ; GO:0006340 to:

term: negative regulation of homeotic gene transcription (Polycomb group) def: Any process that decreases the frequency, rate or extent of transcription from a homeotic gene, by members of the Polycomb group.

and change:

positive regulation of transcription by homeotic gene (trithorax group) ; GO:0006339

to: term: positive regulation of homeotic gene transcription (trithorax group) def: Any process that increases the frequency, rate or extent of transcription from a homeotic gene, by members of the Trithorax group.

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I have checked the biology of these and I'm happy with the decisions, so if everyone else is also happy with this then I'll implement the changes on Thursday 8th May (next Thursday).

Thanks, Jen

Original comment by: jenclark

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Hiya,

Something odd has happened.

I would have obsoleted these terms..

positive regulation of transcription by homeotic gene (Polycomb group) ; GO:0045889
negative regulation of transcription by homeotic gene (trithorax group) ; GO:0045891 regulation of transcription by homeotic gene (Polycomb group) ; GO:0045888 regulation of transcription by homeotic gene (trithorax group) ; GO:0045890.

but the term names have changed since the sourceforge item was submitted and discussed:

positive regulation of transcription of homeotic gene (Polycomb group) ; GO:0045889 negative regulation of transcription of homeotic gene (trithorax group) ; GO:0045891 regulation of transcription of homeotic gene (Polycomb group) ; GO:0045888 regulation of transcription of homeotic gene (trithorax group) ; GO:0045890

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Likewise, I would have made the changes to these terms that Beccy suggests:

Change negative regulation of transcription by homeotic gene (Polycomb group) ; GO:0006340 to:

term: negative regulation of homeotic gene transcription (Polycomb group) def: Any process that decreases the frequency, rate or extent of transcription from a homeotic gene, by members of the Polycomb group.

and change:

positive regulation of transcription by homeotic gene (trithorax group) ; GO:0006339

to: term: positive regulation of homeotic gene transcription (trithorax group) def: Any process that increases the frequency, rate or extent of transcription from a homeotic gene, by members of the Trithorax group.

But the term names have changed.

Change negative regulation of transcription by homeotic gene (Polycomb group) ; GO:0006340

is now

negative regulation of transcription of homeotic gene (Polycomb group) ; GO:0006340

and

positive regulation of transcription by homeotic gene (trithorax group) ; GO:0006339

is now

positive regulation of transcription of homeotic gene (trithorax group) ; GO:0006339

Does anybody know what happened there? Maybe someone else besides me is working on this?

Thanks, Jen

Original comment by: jenclark

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Hiya, I'm not sure why someone's changed these terms so I'm just having a look at the whole set of terms and straightening them out. As far as I can see we need one set of terms for regulation of polycomb and trithorax gene expression and one set of terms for regulation of other genes by polycomb and trithorax activity.

There are currently a number of terms under chromatin remodelling, and they refer to regulation of polycomb and trithorax genes. However, since polycomb and trithorax genes regulate other genes by a mechanism of chromatin remodelling it seems to me that these terms should be the ones that cover regulation by polycomb and trithorax.

Question to Beccy: I just wondered if you would agree with that, or if you know of instances in which polycomb and trithorax genes are also regulated by chromatin remodelling?

If you think that the logic in paragraph two is right then I can change those over and add the following separate terms to cover regulation of polycomb and trithorax gene expression.

New terms:

A) Regulation of Polycomb group gene expression.

1) regulation of transcription of Polycomb group homeotic genes ; GO:new def:Any process that modulates the frequency, rate or extent of transcription of homeotic genes of the Polycomb group.

1) positive regulation of transcription of Polycomb group homeotic genes ; GO:new def: Any process that activates or increases the rate of transcription of homeotic genes of the Polycomb group.

3) negative regulation of transcription of Polycomb group homeotic genes ; GO:new

Definition: Any process that stops, prevents or reduces the rate of transcription of homeotic genes of the Polycomb group.

B) Regulation of Trithorax group gene expression.

1) regulation of transcription of Trithorax group homeotic genes ; GO:new

def:Any process that modulates the frequency, rate or extent of transcription of homeotic genes of the Trithorax group.

2) negative regulation of transcription of Trithorax group homeotic genes ; GO:new

def: Any process that stops, prevents or reduces the rate of transcription of homeotic genes of the Trithorax group.

3) positive regulation of transcription of Trithorax group homeotic genes ; GO:new

def: Any process that activates or increases the rate of transcription of homeotic genes of the Trithorax group.

Ta for the second opinion :-)

Jen

Original comment by: jenclark

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Hi Jen

Just to clarify: you are correct: the terms under c'tin modelling should all refer to regulation OF homeotic genes BY Polcomb/trithorax group proteins. Therefore the text strings at the moment (after their recent revision) are correct, but a little confusing.

To avoid confusion, the text strings (for the two terms that should stay) could be changed to: negative regulation of homeotic gene transcription\, by a Polycomb group member ; GO:0006340 positive regulation of homeotic gene transcription\, by a trithorax group member ; GO:0006339

The defs need tweaking too, as suggested above.

The Polycomb and trithorax group proteins aren't encoded by homeotic genes. They regulate the homeotic genes (changing the text strings of the above GO terms should help sort out this confusion). Therefore I don't think we need 'regulation OF Polycomb/trithorax genes', since as far as I know there is nothing unusual about this process and therefore GO:0006355 could be used.

We need the exisiting regulation OF homeotic genes BY the Polycomb/trithorax group because the transcription is regulated by chromatin modelling, so warrants these specific terms I think.

So I think all that needs doing, is the text sting and definitions for GO:0006339 and GO:0006340 to be changed, and the other 4 terms to be obsoleted..... well that's my view anyway.

Thanks!

Becky

Original comment by: beckyfoulger

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Excellent, thanks. That's what I thought. I'm working on the details right now and will run them by you just as soon as they're ready.

Thanks.

Jen

Original comment by: jenclark

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What do you think about these definitions? Jen

Definitions:

%negative regulation of homeotic gene transcription, by a Polycomb group member ; GO:0006340

def: A process by which Polycomb group genes stop, prevent or reduce the rate of transcription of homeotic genes. In conjunction with Polycomb response elements and promoters, Polycomb group genes convey heritable silenced transcription patterns in an epigenetic manner, on other homeodomain genes. PMID:12628181

positive regulation of homeotic gene transcription, by a Trithorax group member ; GO:0006339

def: A process by which Trithorax group genes activate or increase the rate of transcription of homeotic genes. In conjunction with response elements and promoters, Trithorax group genes convey heritable activated transcription patterns in an epigenetic manner, on other homeodomain genes. PMID:12628181

Original comment by: jenclark

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Hi again,

The PcG and trxG proteins are involved in maintaining the (already established) gene expression of homeotic genes, so could we tweak the definitions to convey that they maintain rather than initiate gene expression.

Also, I like the bit ...'In conjunction - other homeodomain genes'. But if the GO text refers to homeotic gene regulation, then I don't think it should be included. Alternatively, 'homeotic' could be removed from the text string to make a broader term:

eg negative regulation of gene transcription, by a Polycomb group member; GO:0006340 A process by which members of the Polycomb group maintain the inactive state of transcription of genes, including the homeotic genes. In conjunction with Polycomb response elements and promoters, Polycomb group genes convey heritable silenced transcription patterns in an epigenetic manner.

GO:0006339 A process by which members of the trithorax group maintain the active state of transcription of genes, including the homeotic genes. In conjunction with response elements and promoters, trithorax group genes convey heritable activated transcription patterns in an epigenetic manner.

see PMID: 11420721 for revised defs.

Finally, the standard nomenclature seems to be:

Polycomb (ie upper case P) and trithorax (lower case t), so we should stick to this in the text string and definition.

what do you think? Thanks, Becky

Original comment by: beckyfoulger

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Thanks Beccy, those definitions are much better :-)

I've written out the final form ready to be implemented below. If you agree I can do them this afternoon since they're not really controversial and they've been up for comment of ages.

Thanks,

Jen

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Final draft:

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Currently under chromatin remodelling:

%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

The definitions all refer to control of the rate of expression of genes of the Polycomb and trithorax groups by the activity of other gene products. I will change the terms so they refer to control of transcription of other homeodomain genes by Polycomb and trithorax genes.

New version:

%regulation of transcription of homeotic gene (Polycomb group) ; GO:00458888 Comment: This term was made obsolete because only negative regulation occurs. %negative regulation of homeotic gene transcription, by a Polycomb group member ; GO:0006340 %positive regulation of transcription of homeotic gene (Polycomb group) ; GO:0045889 Comment: This term was made obsolete because only negative regulation occurs. %regulation of transcription of homeotic gene (trithorax group) ; GO:0045890 Comment: This term was made obsolete because only positive regulation occurs. %negative regulation of transcription of homeotic gene (trithorax group) ; GO:0045891 Comment: This term was made obsolete because only positive regulation occurs. %positive regulation of homeotic gene transcription, by a trithorax group member ; GO:0006339

Definitions:

%negative regulation of homeotic gene transcription, by a Polycomb group member ; GO:0006340

def: A process by which members of the Polycomb group maintain the inactive state of transcription of genes, including the homeotic genes. In conjunction with Polycomb response elements and promoters, Polycomb group genes convey heritable silenced transcription patterns in an epigenetic manner. PMID:12628181 and PMID: 11420721

positive regulation of homeotic gene transcription, by a trithorax group member ; GO:0006339

def: A process by which members of the trithorax group maintain the active state of transcription of genes, including the homeotic genes. In conjunction with response elements and promoters, trithorax group genes convey heritable activated transcription patterns in an epigenetic manner. PMID:12628181 and PMID: 11420721

Original comment by: jenclark

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Original comment by: jenclark

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Original comment by: jenclark