Change defintion transcription coregulator activity

[pgaudet]

Per @RLovering 's suggestion - to accommodate Mediator subunits, that (presumably) don't all bind to dbTFs. This is likely the case for other coTFs.

New proposed def:

A transcription regulator activity that regulates the activity of a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coregulators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.

@colinlog Thanks, Pascale

[colinlog]

Please keep in mind that eukaryotic genes are intrinsically repressed by nucleosome formation. Mediator's function lies at the border between GTF and co-regulator. I would find 'mediates' much better than 'regulates' if you wish to better accommodate the mediator complex in the dbTF coregulator definition. Can we please look through the Relations Ontology to find an alternative to 'regulates' if 'mediates' is not appropriate? Otherwise, this latest change in the definition brings us back to a very ambiguous definition that will very probably hamper proper annotations to this term. I find it confusing to now explicitly demand that the 'dbTF coregulator' be a 'dbTF regulator', whilst it is primarily a causally linked mechanistic effector, a co-factor for the dbTF even though often the acetyl transferases also feedback on the dbTF to amplify its activity and the deacetylases feedback to repress its activity. The concept is that the dbTF finds the genomic address and then the coregulator performs a 'downstream' molecular function that regulates transcription at that spot on the genome . Binding to the dbTF is not a prerequisite, but performing its transcription regulating function as a consequence of a preceding DNA binding event by a dbTF is. As discussed during the Berkeley jamboree, there are also epigenetic signal transduction cascades that take place at regulatory DNA elements (including self-perpetuating feedback loops) and these often involve covalent histone modifications that are sometimes maintained even in the absence of the initially instigating signal provided by the dbTF DNA binding event. Nevertheless, without the continued presence of dbTFs at a eukaryotic promoter it will not be the source of full length RNA transcripts and it will not therefore need to be repressed more than what nucleosome formation achieves.

Bottom line: I had thought we would refrain just now from calling into life the coregulator's coregulators and would bag all the activities that are recruited by dbTFs as dbTF coregulators. This logic is based on the concept that while the co-regulators may reinforce or enable the activity of a previously marked genomic address (a cis-regulatory transcrition control element like an enhancer or a promoter), it is only the dbTFs that can 'discover' a genomic adress and mark it for transcription activity/inactivity at the hand of enzymtic and other protein complexes that it reruits there and the other molecualr activities that these coregulators recruit or exclude. At some point a distinction must indeed be made between generic chromatin structural proteins (nucleosomes) and those that are coregulators (nucleosome remodelers) as well as the 'epigentic processes that function autonomously, but this will not be made easier by stipulating that coregulators regulate the dbTFs activity. What dbTF coregulators do is to regulate events that lead to RNA polymerase (in)activity after the dbTF has bound the DNA. That explicit spatio-temporally ordered causality relationship which is one of subject and ruler, of hierarchy in the decision making process that makes the DNA binding site the code and the dbTF its reader and the coregulator the helper of the code-reading dbTF has been wiped from the newly proposed version of the coregulator definition, I think.

On Mon, Nov 23, 2020 at 11:05 AM pgaudet notifications@github.com wrote:

Per @RLovering https://github.com/RLovering 's suggestion - to accommodate Mediator subunits, that (presumably) don't all bind to dbTFs. This is likely the case for other coTFs.

New def:

A transcription regulator activity that regulates the activity of a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coregulators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.

@colinlog https://github.com/colinlog Thanks, Pascale

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[pgaudet]

New proposal with @colinlog

A transcription regulator activity that modulates the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coregulators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factors with other transcription coregulators.

Will confirm with @RLovering

[pgaudet]

New coactivator def: GO:0003713

A transcription coregulator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coactivators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator.

New corepressor def: GO:0003714 A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.

New 'nuclear receptor corepressor activity' def GO:0140536 A transcription corepressor activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound nuclear receptor, either on its own or as part of a complex. Nuclear receptor corepressors often act by altering chromatin structure and modifications. For example, one class of transcription nuclear receptor corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.

New 'nuclear receptor coactivator activity' def GO:0030374 A transcription coactivator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound nuclear receptor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator.

[pgaudet]

Another minor change from @colinlog

Replace 'A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.' by A third class modulates interactions of DNA-bound DNA-binding transcription factor with other transcription coregulators.

Thanks, Pascale