IPR003150 regulation of transcription

[ValWood]

• InterPro ID / label

IPR003150

• Example sequences with problematic annotation (ID + gene/protein name):

https://www.pombase.org/gene/SPBC1703.02

• Description of issue

I'm not 100% about this one, but I have annotated RSC complex to

GO:0045815 | transcription initiation-coupled chromatin remodeling

should it also be annotated to
regulation of DNA-templated transcription GO:0006355

@pgaudet
@colinlog

[tony787]

Dear Val,

This InterPro (IPR003150) entry includes a number of mammalian transcription factors such as RFX1/2/3/4/5/6/7/8 for which, as far as I'm aware, the transcription initiation-coupled chromatin remodelling doesn't apply. The RSC complex, on other side, remodels chromatin structure and regulates gene transcription so I believe the term 'regulation of DNA-templated transcription' is applicable to it.

Best wishes,
Toni

[ValWood]

@pgaudet
@colinlog

RSC complex
https://www.pombase.org/term/GO:0016586
regulation or part_of?
The definition is

The RSC complex is generally recruited to RNA polymerase III promoters and is specifically recruited to RNA polymerase II promoters by transcriptional activators and repressors;

which seems like part of? but I'm not sure.

[colinlog]

Because it is recruited by a dbTF it has a MF function as a co-repressor or co-activator and is thus part_of BP transcription regulation.

RSC has a role in generating the dimensions of the nucleosome depleted region of gene promoters (positioning the -1 and + nucleosomes.

Definitely also BP: transcription intitiation-coupled chromatin remodelling.

@pgaudet I notice we deleted the nucleosome sliding/mobilisation BP, but we did not resurect it as a MF... This is certainly what these enzymes do for transcription regulation, more often than not by virtue of being recruited by dbTFs, although they also read the histone modification code.

[ValWood]

This causes a curation logic issue for me.

We are describing the same process in these 2 ways:

if both, this implies that
BP: transcription intitiation-coupled chromatin remodelling.
should be part of regulation of DNA-templated transcription GO:0006355

or are these two annotations describing the role of RSC in 2 different processes, first the regulation, and then the initiation?

[pgaudet]

Looking at this with @colinlog

It looks like you get the hit to IPR003150 based on the PROSITE winged helix domain, which has the annotation to regulation of transcription. This is a bit odd, there is no human ortholog, so it's a bit unusual. Could the winged helix domain be a false positive or a low match?

Colin says RSC is not know to be a sequence-specific dbTF, ie the interpro hit that provides the annotation 'regulation of DNA-templated transcription GO:0006355' seems incorrect.

However the RSC complex is a co-factor recruited by sequence-specific dbTFs, and contributes to making the nucleosome-depleted region on the promoter, where the polymerase will be assembled, so for this role, regulation of DNA-templated transcription GO:0006355' is a correct annotation.

In other words, the annotation is right, but for the wrong reason (ie InterPro).

We can talk about this next Friday if you can join.

[ValWood]

RSC9 seems to have a known DNA binding domain https://www.yeastgenome.org/locus/S000004596/go
in S. cerevisiae (although I don't immediately see DNA binding assay in this paper, which is used for the IDA annotation).

However, Rsc9 pombe and S. cerevisiae appear to have an ARID DNA binding domain based on most protein family methods (Pfam, SMART, CDD) I don't think this is a false positive for the family.

My main issue here is that we describe the same process with 2 3 different terms in 2 different parts of the graph.
In the GO context, it doesn't seem that the remodelled is doing the regulating? The transcription factor is doing this?)
Presumably the initiation-associated remodelling is required for the transcription to occur as much as the polymerase?
I can join next Friday.

[ValWood]

I forgot to respond to this.

The outcome is that RSC is a co-regulator and so it has 2 roles,
i) as a coregulator for regulation of initiation and ii) as part of transcription initiation-coupled chromatin remodeling

SO the mappings are OK.