child term for GO:0001191 RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription

[gocentral]

Hi

please would you add the child term

GO:0001191 RNA polymerase II activating transcription factor binding transcription factor activity involved in negative regulation of transcription Definition: Interacting selectively and non-covalently with an RNA polymerase II activating transcription factor and also with the RNA polymerase II basal transcription machinery in order to stop, prevent, or reduce the frequency, rate or extent of transcription.

narrow synonym: RNA polymerase II transcription repressor activity

as an is_a child of GO:0001191 RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Note the definition used is from that of the suggested existing sibling: GO:0001106 RNA polymerase II transcription corepressor activity

Thanks

Ruth

Reported by: RLovering

Original Ticket: geneontology/ontology-requests/11712

[gocentral]

Hi Ruth,

Is there a pasto in the ticket? Reads like you want me to make GO:0001191 an is_a child of itself.

Cheers, David

Original comment by: dosumis

[gocentral]

• assigned_to: David Osumi-Sutherland

Original comment by: dosumis

[gocentral]

Hi David yes sorry working too early this morning.

NEW GO term: RNA polymerase II activating transcription factor binding transcription factor activity involved in negative regulation of transcription Definition: Interacting selectively and non-covalently with an RNA polymerase II activating transcription factor and also with the RNA polymerase II basal transcription machinery in order to stop, prevent, or reduce the frequency, rate or extent of transcription.

narrow synonym: RNA polymerase II transcription repressor activity

as an is_a child of GO:0001191 RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription

Note the definition used is from that of the sibling: GO:0001106 RNA polymerase II transcription corepressor activity

Thanks

Ruth

Original comment by: RLovering

[gocentral]

Can you think of a viable shorter name? This one makes my head spin.

Original comment by: dosumis

[gocentral]

RNA polymerase II transcription repressor activity?

All of the transcription factor terms make my head spin. I don't know why we don't use the names that biologists use.....

Original comment by: ValWood

[gocentral]

RNA polymerase II transcription repressor activity?

Sounds good, but I notice that Ruth has this as a narrow synonym. In what sense is it narrow?

All of the transcription factor terms make my head spin. I don't know why we don't use the names that biologists use.....

+1

Original comment by: dosumis

[gocentral]

Looking at this further, this appears to be a broad synonym - it at least applies to the parent class - and is tagged as a broad synonym for that.

Original comment by: dosumis

[gocentral]

A compromise:

RNA polymerase II transcription factor binding transcription repressor activity RNA polymerase II activating transcription factor binding transcription repressor activity

???

Original comment by: dosumis

[gocentral]

For this compromise to work more broadly, we'd need a new name for

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Perhaps

RNA polymerase II transcription factor binding transcription activator activity ??

(http://en.wikipedia.org/wiki/Activator_(genetics))

Original comment by: dosumis

[gocentral]

Hi

I completely agree, we should be aiming for terms used by scientists, as also suggested in Barcelona by Suzie.

However, it was explained to me, by Karen, on Tuesday that it is not possible to have a MF GO term for TF repressor activity and that these proteins should instead be annotated to the BP term GO:0001227 - RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription (or parents terms).

I was therefore looking to create a specific activity to describe the activity of cystin in PMID:24349431 (one of the annotation consistency papers)

I therefore suggested the narrow synonym because I didn't like to suggest that this was an exact synonym.

Looking at a couple of reviews: PMID:12785719 and PMID:24418103, I think we perhaps should aim to have a series of repressing terms to enable the various different repressing activities to be specifically defined and reduce inappropriate use.

See

PMID:24418103 describes: Mechanisms of transcriptional repression can be divided into three categories;

1. inhibition of the basal transcriptional machinery: repressors that interfere with the binding of RNA polymerase, TATA box-binding protein, and/or general transcription factors to transcription start sites; thus, preventing transcription initiation
2. ablation of transcriptional activator function: repressors targeting transcriptional activators and co-activators, resulting in their degradation, nuclear export, or inhibiting their ability to bind DNA.
3. remodeling of chromatin : recruitment of chromatin remodeling factors, which cause epigenetic alterations on the genome.

Plus 4: non-coding RNAs in transcriptional repression by interacting with chromatin modifying factors (Wang et al., 2010).

PMID:12785719 describes: General repression: General repressor protein (or complex) either sequesters or modifies a central component of the Pre-initiation complex (PIC) or RNA polymerase II. Thus general repressor will down-regulate expression of all genes transcribed by this RNA polymerase. Eg 1: Phosphorylation of RNA polymerase core subunit by herpes virus ICP22, UL13 kinases, which generates a non-functional polymerase and general repression[ ref 14]. Eg 2: Nucleosomes generally repress promoter activity by sequestering promoter DNA into chromatin [ref 15].

Gene-specific repression: Gene-specific repressors act by decreasing the concentration of a functional activator/co-activator at the promoter or by counteracting the stimulatory effect of these proteins on transcription. In addition, some repressors inhibit transcription by interacting in a promoter-specific fashion with components of the PIC or by recruiting chromatin-remodelling proteins. Gene-specific repressors may: Bind directly or indirectly to DNA,

Regulate transcription from binding sites proximal [short-range repressors] or at a distance [long-range repressors] from the promoter [ref 16].

So considering the type of experiments we are annotating would it be possible to create MF terms with sensible names to represent these different classes of proteins?

Firstly do we have to have ‘RNA polymerase II’ included in the name, as the ontology will provide this information, and this can be included in the exact synonym? If this can be removed we could have: NEW GO Term 1. General transcription repressor activity (provide more specific terms as the data is annotated?) Exact synonyms: RNA polymerase II general transcription repressor activity

NEW GO Term 2. Transcription factor binding repressor activity Exact synonyms: Transcription factor binding gene-specific transcription repressor activity; RNA polymerase II transcription factor binding gene-specific transcription repressor activity

NEW GO Term 3 From initial inquiry and child of NEW GO Term 2 above: activating transcription factor binding repressor activity Exact synonyms: RNA polymerase II activating transcription factor binding transcription factor activity involved in negative regulation of transcription; Activating transcription factor binding gene-specific transcription repressor activity; RNA polymerase II activating transcription factor binding gene-specific transcription repressor activity

NEW GO Term 4. DNA binding transcription repressor activity Exact synonyms: DNA binding transcription gene-specific transcription repressor activity; Gene-specific DNA binding RNA polymerase II transcription repressor activity

NEW GO Term 5. Pre-initiation complex binding transcription repressor activity Exact synonyms: Pre-initiation complex binding gene-specific transcription repressor activity; Gene-specific Pre-initiation complex RNA polymerase II transcription repressor activity

NEW GO Term 6. Transcription repressor activity by regulation of chromatin-remodeling Exact synonyms: Gene-specific transcription repressor activity by regulation of chromatin-remodeling; Gene-specific RNA polymerase II transcription repressor activity by regulation of chromatin-remodeling

Note that several repressors will be annotated to more than one of these functions. Plus the definitions would have to make it clear that these are repressing terms and not for co-repressing terms.

I am happy to help sort out definitions for these if the concept is agreed. In addition, this should be discussed with the transcription factor group in Norway.

Best

Ruth

Original comment by: RLovering

[gocentral]

Hi David

sorry my comments took a long time to write and I missed your comments.

Yes all of your suggestions sound great to me.

Ruth

Original comment by: RLovering

[gocentral]

Hi Ruth,

However, it was explained to me, by Karen, on Tuesday that it is not possible to have a MF GO term for TF repressor activity

I've never been convinced that the rest of the world cares about strict interpretations of MF...

From a quick look through, your general proposal looks great. But it will clearly require some wider agreement, so I'd like to make this comment into a separate ticket (on JIRA (?)) for more generally discussion before implementing.

For this ticket, would you be happy with my suggested compromise names above?

I've provisionally used these in my working copy of the ontology, but could easily switch back for now. I've also added logical definitions for your new term and bunch of similar ones. These are already doing some useful work in autoamting classification and are useful breakdown (for me at least) of the meaning of these terms.

Cheers, David

Original comment by: dosumis

[gocentral]

Oops. Comments crossed again. I'll go ahead and commit with my new names and see who yells. Will also put your broader suggestion on a JIRA ticket.

Cheers again, David

Original comment by: dosumis

[gocentral]

• status: open --> closed-fixed

Original comment by: dosumis

[gocentral]

Solution:

GO_0001191 label "RNA polymerase II transcription factor binding transcription repressor activity" has_broad_synonym "RNA polymerase II transcription repressor activity" has_exact_synonym "RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription" EquivalentTo: 'protein binding transcription factor activity' that ('has part' some 'RNA polymerase II transcription factor binding') and ('part of' some 'negative regulation of transcription from RNA polymerase II promoter')

GO_0098811 label "RNA polymerase II activating transcription factor binding transcription repressor activity" definition "Interacting selectively and non-covalently with an RNA polymerase II activating transcription factor and also with the RNA polymerase II basal transcription machinery in order to stop, prevent, or reduce the frequency, rate or extent of transcription." has_broad_synonym "RNA polymerase II transcription repressor activity" has_exact_synonym "RNA polymerase II activating transcription factor binding transcription factor activity involved in negative regulation of transcription" has_obo_namespace "molecular_function" EquivalentTo: 'protein binding transcription factor activity' that ('has part' some 'RNA polymerase II activating transcription factor binding') and ('part of' some 'negative regulation of transcription from RNA polymerase II promoter')

Closing for now.

Original comment by: dosumis