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TFIID subunits TAFII are general TFs and should be direct to transcription and not to "regulation of" (unless subunits that are shared with SAGA) #2944

Closed ValWood closed 1 year ago

ValWood commented 4 years ago

applies to TAF2 Q6P1X5 (human) , TAF4 O00268 (human)

annotation should be

ValWood commented 4 years ago

could not query this one in p2GO

TAF2

TAF4

ValWood commented 4 years ago

TAF3

Overexpression of TAF3 decreases the level of p53 protein but not p53 mRNA

Not sure about this...but it isn't regulation of transcription. As it is an overexpression it could just be causing problems more generally

ValWood commented 4 years ago
ValWood commented 4 years ago

For most of the annotations I have looked at, it seems to make sense to move from 'regulation of txn' to 'txn'

However, there seems to be a bunch of publications relating TAFs to the specific negative regulation of transcription of some p53 associated TF. I flagged these publications in the spreadsheets for discussion.

ValWood commented 4 years ago

Some TFIID subunits are also SAGA (e.g TAF9). I forgot about this. So Taf9 is also a co-activator. This might account for the regulation annotations,

ValWood commented 4 years ago

I really think we have created a problem introducing the role like grouping terms like GTF, co-repressor etc into the function ontology. I still think that these a really 'process' groupings and not describing activities.

It's making annotation quite difficult because it is grouping disparate functions, its really a "process grouping in the MF ontology"

Can we discuss this today?

ValWood commented 4 years ago

@pgaudet for the ones I could not challenge in P2GO

ValWood commented 4 years ago

TAF1 UniProtKB:P21675, I raised a dispute about this but it is similar to the ones I tagged in the spreadsheet. Seems to have a specific role in "Phosphorylates TP53 on 'Thr-55' which leads to MDM2-mediated degradation of TP53"

reactome used regulation of signal transduction by p53 class mediator

and this might be where these come from

negative regulation of DNA-binding transcription factor activity Source: BHF-UCL negative regulation of gene expression Source: ParkinsonsUK-UCL negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding negative regulation of ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL positive regulation of transcription by RNA polymerase II Source: BHF-UCL positive regulation of transcription initiation from RNA polymerase II promoter Source: BHF-UCL regulation of transcription, DNA-templated Source: ParkinsonsUK-UCL

regulation of transcription initiation from RNA polymerase II promoter Source: ParkinsonsUK-UCL transcription factor catabolic process Source: ParkinsonsUK-UCL GO:2000825  positive regulation of androgen receptor activity ECO:0000314 IDA PMID:20181722   9606 Homo sapiens ParkinsonsUK-UCL part_of (GO:0071383) more...

My feeling is that the role in initiation is direct, not regulatory, but that it has another role in turning off the p53 dept0transcription. I can't figure if this is regulation or

ValWood commented 4 years ago

https://en.wikipedia.org/wiki/Transcription_factor_II_D

I think it comes down to how we capture "acts as a channel for regulatory signals"

A nice new paper about TFIID in Cell reports https://www.sciencedirect.com/science/article/pii/S2211124719300208 Multivalent Role of Human TFIID in Recruiting Elongation Components at the Promoter-Proximal Region for Transcriptional Control

ValWood commented 4 years ago

@colinlog What are your thoughts about TAF1. I got very bogged down in this one. Is this a good example? Are we conflating "receiving the signal from the Db-TF" with "regulation"?

colinlog commented 4 years ago

This needs to be discussed. For now, TFIID subunits will first get the GTF annotation, just following the rules that stem from the community.

On Wed, Apr 29, 2020 at 9:50 AM Val Wood notifications@github.com wrote:

@colinlog https://github.com/colinlog What are your thoughts about TAF1. I got very bogged down in this one. Is this a good example? Are we conflating "receiving the signal from the Db-TF" with "regulation"?

— You are receiving this because you were mentioned. Reply to this email directly, view it on GitHub https://github.com/geneontology/go-annotation/issues/2944#issuecomment-621045321, or unsubscribe https://github.com/notifications/unsubscribe-auth/ALZVLKGMVV7A7PM7PGXUDKLRO7L3JANCNFSM4MS4ZLHQ .

ValWood commented 4 years ago

But there are existing annotations to "regulation of transcription" I though the point of the exercise was to validate or refute these?

This also looks useful for the mechanism of the p53 connection, although quit old https://www.ncbi.nlm.nih.gov/pubmed/17996705 This just seems like "recruitment" to me. It doesn't look like TFIID is doing the regulating. P53 is the regulator, and the things which do the PT modifications....

colinlog commented 4 years ago

Later, we could add other annotations for individual subunits? The discussion as to processes and functions is very interesting to have, and it also pertains to annotation of complexes versus their individual subunits, which is really what you are on about here Val, isn't it? Let's not rush it. TFIID is a well accepted and deeply conserved TBP complex that binds eukaryotic promoters and it is an accepted paradigm for GTFs. SAGA and the other GCN5/PCAF HAT complexes are functionally related, but do not harbour TBP. Also p300/CBP is an interesting case.

ValWood commented 4 years ago

I thought we were working through the spreadsheet and resolving where gene products were annotated to both "transcription" and "regulation of transcription". TAFs , which are GTFs, according to yesterdays discussion have many annotations to "regulation of transcription", so these need to be resolved as part of the exercise. Did I misunderstand what we were supposed to be doing?

ValWood commented 4 years ago

So in summary, TAF1 appers to have an additional. role in phosphorylation and negatively regulating DBTF binding (p53)

RLovering commented 4 years ago

TAF3

* [ ]  Q5VWG9 | TAF3 |   | GO:0000122 | negative regulation of transcription by RNA polymerase II | ECO:0000314(IDA) | ECO:0000314 | (IDA) |   | PMID:18549481

Overexpression of TAF3 decreases the level of p53 protein but not p53 mRNA

Not sure about this...but it isn't regulation of transcription. As it is an overexpression it could just be causing problems more generally

HI Val, the title of this paper is: TATA binding protein associated factor 3 (TAF3) interacts with p53 and inhibits its function. As p53 pos reg expression of lots of genes I think this annotation (TAF3 neg reg transcription) is OK

ValWood commented 4 years ago

Yes agreed.

SO the GTF annotatins sholdcouple with "transcription initiation" (no regulation

and the p53 related ones are negative regulation of transcription

pgarmiri commented 4 years ago

The UniProt annotations have been fixed. Thanks, Penelope

marcfeuermann commented 1 year ago

Looks like that this has been addressed during the transcription refactoring project.