PTHR46138 - PANTHER:PTN000115754

[ValWood]

Based on @colinlog comments here: https://github.com/pombase/curation/issues/2707 ncb2 should not be annotated to co-repressor

ncb2 | transcription corepressor Ncb2 (predicted) |   | transcription corepressor activity |   | GO_Central | Schizosaccharomyces pombe | IBA | CGD:CAL0000180502 PANTHER:PTN000115754 SGD:S000002805 | protein dr1 pthr46138 | protein |   | PMID:21873635 | 20180115

@pgaudet @srengel

[ValWood]

also applies to

bur6 | transcription regulator complex subunit Bur6 (predicted) |   | transcription coregulator activity |   | GO_Central | Schizosaccharomyces pombe | IBA | MGI:MGI:1913806PANTHER:PTN000028883 SGD:S000000961 | histone-like transcription factor ccaat-related pthr10252 | protein |   | PMID:21873635

https://github.com/pombase/curation/issues/2309

[pgaudet]

After discussion with @colinlog and @ValWood , we decided that this was a GTF, because it acts at the core of every promoter and is required for activated transcription to take place. We dont feel it is necessary to create a new term right now.

[pgaudet]

@srengel @marekskrzypek cyn aou please fix your EXP annotations from co-regulator to GO:0016251 RNA polymerase II general transcription initiation factor activity

S000002805

and CAL0000180502

Thanks, Pascale

[marekskrzypek]

CGD done

[srengel]

Hi @pgaudet i think that changing all the co-repressor to general transcription initiation factor is not really the right thing to do.

in yeast this protein is important for NOT having promiscuous cryptic transcription, so the annotation changes you are requesting don't really work for S.cerevisiae.

https://www.yeastgenome.org/reference/S000183142

[ValWood]

I already changed my ncb2 to RNA polymerase II general transcription initiation factor activity Ncb2 is a special case....but @colinlog can you explain more detail the rationale why it is GTF (it's also confusing because the complex is called [negative cofactor 2 complex GO:0017054)]

The justification from https://github.com/pombase/curation/issues/2707 was in this comment https://github.com/pombase/curation/issues/2707#issuecomment-646604183

but we need to make sure that everyone is using the same term. It will be weird for yeast to use one term and metazoans another term.

I appreciate that ncb2 is different from co-repressors but I'm not sure it will be clear to curators why this would be a GTF.

[pgaudet]

Thanks for the feedback @srengel

I'll check with @colinlog again

[ValWood]

Also, might need to revisit the mapping https://github.com/geneontology/go-annotation/issues/3412#issuecomment-1373716233

[pgaudet]

@colinlog says that ncp2 also has a role in recycling TBP for use in further transcription events, so it also serves to promote transcription. The paper states

CONCLUSIONS: We conclude that NC2 plays a general role in transcription initiation in RNA polymerase II genes that is related with its known TBP interchange function

While it negatively regulates transcription, it does not function as a co-repressor - and as far as we can tell, the authors don't describe this gene as a co-repressor.

[marcfeuermann]

This has been reviewed by Pascale in PAINT 2 months ago.

[ValWood]

@pgaudet can you confirm the term we should be using here. I'm not sure that we got closure on this ?

[pgaudet]

I do have this on my Friday transcription call list of discussion topics. Hopefully this week we can get to it!

[colinlog]

Dear All, Yes, it is as stated in Pascale's last comment here.

@srengel It is certainly NOT that we propose to change "all the co-repressor to general transcription initiation factor" !!! Only the ncp2 co-repressor term.

For clarity: co-repressor and co-activator are currently defined as proteins recruited by sequence-specific transcription factors to gene enhancers and promoters to modulate their transcription rate. Since TBP is a GTF and it 'recruits' ncp2 so as to be recycled towards any other promoter (cryptic or not) we propose to consider that ncp2 is part of the GTF protein set (see also figure 1 of PMID: 25957681). NC2 helps to 'read' the strength of a promoter at the DNA level. Cryptic promoters are quite bad at recruiting TBP (within a Mot1 complex, a TFIIA complex or a TFIID complex) and ncp2 therefore appears to repress them, in the sense that when it is absent TBP bind there better and there is more transcription from cryptic promoters. However, at such cryptic promoters, it is very doubtfull that there is a sequence-specific DNA binding transcription factor that actively recruits ncp2 to remove TBP and therefore make it act as a co-repressor for such a hypothetic dbTF that would antagonise cryptic promoter activity.

It is therefore a little mysterious to me why S.c. labels ncp2 as a co-repressor. GTF repressor would be fine, but it does not quite cover the function, which is also to increase TBP mobility from one TSS to another, just like mot1.

Altogether, the argument is that ncp2 is a GTF in the sense that it enables TBP recruitement to the next promoter it should act on, but it does it in trans, by mobilising TBP away from 'weak' promoters, recylcing it as it were.

Thus, ncp2 has a positive influence on transcription initiation and participates in homeostasis based on genomic DNA transcription start sites (TSS) / transcription initiation sites.

Does this help motivating the annotation change for S.c @srengel ?

Pascal and I will re-discuss this tomorrow afternoon during the transcription call

[pgaudet]

@srengel are we all good with this one?

[pgaudet]

Fixed family, please reopen if needed