Edits to transcription regulator definitions

[pgaudet]

While working on the transcription guidelines paper we have noticed some inconsistencies with the refactored transcription regulator definitions and subclasses.

@colinlog @RLovering and I have made the following changes:

• GO:0140223 general transcription initiation factor activity -> changed subclass from 'GO:0140110 transcription regulator activity' to 'GO:0003674 molecular_function'. This way, 'general transcription initiation factor activity' is part of 'GO:0006351 transcription, DNA templated', while 'transcription regulator activity' is part of 'GO:0006355 regulation of transcription, DNA templated'. Transcription regulators are not MF regulators, they are regulators of BP (transcription).

• GO:0003712 coTF: added parent 'molecular function regulator' since coTFs do directly regulate various MFs.

[pgaudet]

Newer changes are in the comment below: https://github.com/geneontology/go-ontology/issues/20253#issuecomment-721633471

---

OLD :

Changes to definitions:

mf	label	curent definition	Proposed new def Pascale/Colin/Ruth Nov 3	Comment
GO:0140110	transcription regulator activity	A molecular function that controls the rate, timing and/or magnitude of transcription of genetic information. The function of transcriptional regulators is to modulate gene expression at the transcription step so that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism.	A molecular function that controls the rate, timing and/or magnitude of gene transcription. The function of transcriptional regulators is to modulate gene expression at the transcription step so that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism. Genes are transcriptional units, and include bacterial operons.
GO:0003700	DNA-binding transcription factor activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.	A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to modulate transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units. // Curator guidance: Note that most DNA-binding transcription factors do not have enzymatic activity. The presence of specific DNA-binding domains known to be present in DNA-binding transcription factors (HOX, GATA etc) should be used to help decide whether a protein is a DNA binding transcription factor or a coregulator. If a protein has an enzymatic activity (for example, ubiquitin ligase, histone acetyl transferase) and no known DNA binding domain, consider annotating to GO:0003712 transcription coregulator activity. Special care should be taken with proteins containing inc fingers, Myb/SANT and ARID domains, since only a subset of proteins containing these domains directly and selectively bind to regulatory DNA motifs in cis-regulatory regions.
GO:0001216	DNA-binding transcription activator activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence in order to activate or increase the frequency, rate or extent of transcription by a RNA polymerase.	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to activate or increase transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0001217	DNA-binding transcription repressor activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence in order to stop, prevent, or reduce the frequency, rate or extent of transcription by a RNA polymerase.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific gene sets.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0001227	DNA-binding transcription repressor activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to repress or decrease transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific gene sets transcribed by RNA polymerase II.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0106250	DNA-binding transcription repressor activity, RNA polymerase III-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase III-transcribed gene to repress or decrease transcription.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific sets of non-coding RNA genes transcribed by RNA polymerase III.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0098531	ligand-activated transcription factor activity	A DNA-binding transcription factor activity that is directly regulated by binding of a ligand to the protein with this activity. Examples include the lac and trp repressors in E.coli and many steroid hormone receptors.	A DNA-binding transcription factor activity regulated by binding to a ligand and that modulates the transcription of specific gene sets. Examples include the lac and trp repressors in E.coli and steroid hormone receptors.	DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0004879	nuclear receptor activity	A DNA-binding transcription factor activity regulated by binding to a ligand that modulates the transcription of specific gene sets transcribed by RNA polymerase II. The ligand is usually lipid-based (such as a steroid hormone) and the binding of the ligand to its receptor often occurs in the cytoplasm, and the complex is translocated to the nucleus. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	Note that for nuclear receptors, the motif is most often referred to as a response element. DNA-binding transcription factors bind to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.
GO:0003712	transcription coregulator activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to either activate or repress the transcription of specific genes. 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 ATP-dependent class modifies the conformation of chromatin. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.	A transcription regulator activity that modulates the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	Curator guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0003713	transcription coactivator activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to activate the transcription of specific genes. 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 ATP-dependent class modifies the conformation of chromatin. Another type of coregulator activity is the bridging of a DNA-binding transcription factor to the basal transcription machinery. The Mediator complex, which bridges transcription factors and RNA polymerase, is also a transcription coactivator.	A transcription coregulator activity that activates or increases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	Curator guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0030374	nuclear receptor transcription coactivator activity	The function of a transcription cofactor that activates transcription in conjuction with a ligand-dependent nuclear receptor from a RNA polymerase II promoter; does not bind DNA itself.	A transcription coregulator activity that activates or increases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound nuclear receptor. 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. 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.	Curator guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0003714	transcription corepressor activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to repress the transcription of specific genes. Corepressors 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 ATP-dependent class modifies the conformation of chromatin. A third class occludes DNA-binding transcription factor protein-protein interaction domains. A fourth class of corepressors prevents interactions of DNA bound DNA-binding transcription factor with coactivators.	A transcription coregulator activity that represses or decreases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	Curator guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0140536	nuclear corepressor activity	NEW	A transcription corepressor activity that represses or decreases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound nuclear receptor. 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.	Curator guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0140223	general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation.	A molecular function that contributes to transcription start site selection and transcription initiation.
GO:0001181	RNA polymerase I general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase I. Factors required for RNA polymerase I transcription initiation include upstream activation factor (UAF), core factor (CF), TATA binding protein (TBP) and RRN3.	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase I. Factors required for RNA polymerase I transcription initiation include upstream activation factor (UAF), core factor (CF), TATA binding protein (TBP) and RRN3.
GO:0016251	RNA polymerase II general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase II. The general transcription factors for RNA polymerase II include TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TATA-binding protein (TBP).	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase II. The general transcription factors for RNA polymerase II include TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TATA-binding protein (TBP).
GO:0000995	RNA polymerase III general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase III. Factors required for RNA polymerase III transcription initiation include TFIIIA, TFIIIB and TFIIIC.	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase III. Factors required for RNA polymerase III transcription initiation include TFIIIA, TFIIIB and TFIIIC.

[pgaudet]

@krchristie @cmungall @ukemi @hdrabkin @balhoff @deustp01 @vanaukenk

Following up on yesterday's ontology call - those are the definitions I propose to implement for the transcription regulators. Please let me know if you have comments/suggestions.

Thanks, Pascale

[krchristie]

I have a few comments:

1. DNA-binding transcription repressor activity, RNA polymerase III-specific (GO:0106250)

• I don't know if any exceptions to the generalization that RNAP III ONLY transcribes non-coding RNA genes, but considering that there is a known exception to the generalization that RNAP I ONLY transcribes rRNA genes, it seems like it might not be a good idea to write the type of target genes into the definition in an absolute way. So, if you wish to include that info (and you haven't added it in the new def for the other RNAP III term you list here, RNA polymerase III general transcription initiation factor activity (GO:0000995), how about adding it as an extra phrase rather than as an absolute, perhaps like this:
• From: A DNA-binding transcription factor activity that represses or decreases the transcription of specific sets of non-coding RNA genes transcribed by RNA polymerase III.
• To: A DNA-binding transcription factor activity that represses or decreases the transcription of specific genes or genes sets (usually non-coding RNA genes) transcribed by RNA polymerase III.
  2. gene vs gene set
• Does every transcription factor regulate multiple genes, or are there some very specific ones that might regulate only a single gene? Basically I am wondering if it might be better to be more broad, perhaps like this:
• From: "the transcription of specific gene sets"
• To: "the transcription of specific genes or gene sets"
  3. missing proposed new def?
• nuclear receptor activity (GO:0004879) - The text in new def column seems to be the comment, not the proposed new def.

[colinlog]

For the nuclear receptors (GO:00004879) three points to be made. Firstly, the part "and the binding of the ligand to its receptor often occurs in the cytoplasm, and the complex is translocated to the nucleus" is only true for some of the members of the 'Nuclear Receptor subfamily 3 such as the glucocorticoid, mineralocorticoid, androgen and progesterone receptors. Estrogen receptor (NR3A1) is know to be in the nucleus even without it's ligand. Importantly, the nuclear receptors subfamily 1 members such as RAR, TR, LXR, etc. are known to be bound to DNA together with RXR also when none of these have a bound ligand, and in that conformation they are transcription repressors. All this to propose to delete this specification from the definition. A second point is that this term is about a protein family that is defined at the protein sequence level by a C4 type zinc finger and a ligand binding domain and that could be stated in the definition. A third point is that there are members of this family that are 'orphans' in the sense that they have no known ligand, and may even not have one at all. Hence, the ligand part of the definition. must be qualified as 'usually' so as to permit the so-called orphan nuclear receptors to fit the definition. Thanks, Colin

[pgaudet]

Deleted previous comment - adding again with corrections

[pgaudet]

Thanks for the feedback @krchristie

1. DNA-binding transcription repressor activity, RNA polymerase III-specific (GO:0106250)

I will remove non-coding RNA from the definition (A DNA-binding transcription factor activity that represses or decreases the transcription of specific sets of ~non-coding RNA~ genes transcribed by RNA polymerase III.).

On the other hand, I will add to the definition of GO:0000995 | RNA polymerase III general transcription initiation factor activity

• RNA polymerase III transcribes genes encoding short RNAs, including tRNAs, 5S rRNA, U6 snRNA, the short ncRNA component of RNases P, the mitochondrial RNA processing (MRP) RNA, the signal recognition particle SRP RNA, and in higher eukaryotes a number of micro and other small RNAs.
• Def xref: PMID:27068803, PMID:20413673

---

Similarly for RNA pol I and pol II

GO:0001181 RNA polymerase I general transcription initiation factor activity

• Add to the definition: RNA polymerase I transcribes the three largest rRNAs, 5.8S, 18S, and 28S.
• Add Def xref:PMID: 31358304, PMID: 25346433

GO:0016251 RNA polymerase II general transcription initiation factor activity

• Add to the definition: RNA polymerase II transcribes all messenger RNAs (mRNAs) and most regulatory, untranslated RNAs.
• Def xref: PMID: 23442138

[pgaudet]

Although those additions feel like thy are on the wrong terms - should they not rather be on the respective RNA polymerase activities themselves ??

[pgaudet]

2. gene vs gene set

I see what you mean, your formulation is more precise, but given that a set can contain a single item, I prefer the simpler formulation, also because it makes the definition easier to understand.

[pgaudet]

New definitions based on feedback from @krchristie and @thomaspd

mf	label	curent definition	Proposal Pascale/Colin/Ruth Nov 3	Comment
GO:0140110	transcription regulator activity	A molecular function that controls the rate, timing and/or magnitude of transcription of genetic information. The function of transcriptional regulators is to modulate gene expression at the transcription step so that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism.	A molecular function that controls the rate, timing and/or magnitude of gene transcription. The function of transcriptional regulators is to modulate gene expression at the transcription step so that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism. Genes are transcriptional units, and include bacterial operons.	NA
GO:0003700	DNA-binding transcription factor activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.	A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.	Usage guidance: Most DNA-binding transcription factors do not have enzymatic activity. The presence of specific DNA-binding domains known to be present in DNA-binding transcription factors (HOX, GATA etc) should be used to help decide whether a protein is a DNA binding transcription factor or a coregulator. If a protein has an enzymatic activity (for example, ubiquitin ligase, histone acetyl transferase) and no known DNA binding domain, consider annotating to GO:0003712 transcription coregulator activity. Special care should be taken with proteins containing zinc fingers, Myb/SANT and ARID domains, since only a subset of proteins containing these domains directly and selectively bind to regulatory DNA motifs in cis-regulatory regions.
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to modulate transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0001216	DNA-binding transcription activator activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence in order to activate or increase the frequency, rate or extent of transcription by a RNA polymerase.	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to activate or increase transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0001217	DNA-binding transcription repressor activity	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence in order to stop, prevent, or reduce the frequency, rate or extent of transcription by a RNA polymerase.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific gene sets.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0001227	DNA-binding transcription repressor activity, RNA polymerase II-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase II-transcribed gene to repress or decrease transcription. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific gene sets transcribed by RNA polymerase II.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0106250	DNA-binding transcription repressor activity, RNA polymerase III-specific	Interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within the regulatory region of a RNA polymerase III-transcribed gene to repress or decrease transcription.	A DNA-binding transcription factor activity that represses or decreases the transcription of specific genes sets transcribed by RNA polymerase III.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0098531	ligand-activated transcription factor activity	A DNA-binding transcription factor activity that is directly regulated by binding of a ligand to the protein with this activity. Examples include the lac and trp repressors in E.coli and many steroid hormone receptors.	A DNA-binding transcription factor activity regulated by binding to a ligand and that modulates the transcription of specific gene sets. Examples include the lac and trp repressors in E.coli and steroid hormone receptors.	For usage guidance, see comment in GO:0003700 ; DNA-binding transcription factor activity.
GO:0004879	nuclear receptor activity	Combining with a signal and transmitting the signal to the transcriptional machinery by interacting selectively and non-covalently with a specific double-stranded genomic DNA sequence in order to modulate transcription by RNA polymerase II.	A DNA-binding transcription factor activity regulated by binding to a ligand that modulates the transcription of specific gene sets transcribed by RNA polymerase II. Nuclear receptor ligands are usually lipid-based (such as a steroid hormone) and the binding of the ligand to its receptor often occurs in the cytoplasm, which leads to its tranlocation to the nucleus.	Usage guidance: Nuclear receptors are a protein family defined by the presence of a C4-type zinc finger DNA-binding domain and a ligand binding domain. For nuclear receptors, the DNA binding motif is most often referred to as a response element. GO:0004879 is intended for annotation of nuclear receptors that regulate transcription by binding directly to DNA. When the nuclear receptor functions by binding to other transcription factors or transcription factor complexes, consider instead annotating to 'GO:0030374 ; nuclear receptor transcription coactivator activity' or GO:0140536 ; nuclear corepressor activity.
xxxxxx	xxxxxx	xxxxxx	xxxxxx	xxxxxx
GO:0003712	transcription coregulator activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to either activate or repress the transcription of specific genes. 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 ATP-dependent class modifies the conformation of chromatin. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.	A transcription regulator activity that modulates the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	Usage guidance: Most transcription coregulators do not bind DNA. Those that do usually bind DNA either in a non-specific or non-direct manner. If a protein binds DNA specifically, consider annotating to GO:0003700 DNA binding transcription factor activity.
GO:0003713	transcription coactivator activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to activate the transcription of specific genes. 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 ATP-dependent class modifies the conformation of chromatin. Another type of coregulator activity is the bridging of a DNA-binding transcription factor to the basal transcription machinery. The Mediator complex, which bridges transcription factors and RNA polymerase, is also a transcription coactivator.	A transcription coregulator activity that activates or increases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	For usage guidance, see comment in GO:0003712 ; transcription coregulator activity.
GO:0030374	nuclear receptor transcription coactivator activity	The function of a transcription cofactor that activates transcription in conjuction with a ligand-dependent nuclear receptor from a RNA polymerase II promoter; does not bind DNA itself.	A transcription coactivator activity that activates or increases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound nuclear receptor. 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.	For usage guidance, see comment in GO:0003712 ; transcription coregulator activity.
GO:0003714	transcription corepressor activity	A protein or a member of a complex that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to repress the transcription of specific genes. Corepressors 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 ATP-dependent class modifies the conformation of chromatin. A third class occludes DNA-binding transcription factor protein-protein interaction domains. A fourth class of corepressors prevents interactions of DNA bound DNA-binding transcription factor with coactivators.	A transcription coregulator activity that represses or decreases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound DNA-binding transcription factor. 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.	For usage guidance, see comment in GO:0003712 ; transcription coregulator activity.
GO:0140536	nuclear corepressor activity	NEW	A transcription corepressor activity that represses or decreases the transcription of specific gene sets via selective and non-covalent binding to a DNA-bound nuclear receptor. 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.	For usage guidance, see comment in GO:0003712 ; transcription coregulator activity.
xxxxxx	xxxxxx	xxxxxx	xxxxxx	xxxxxx
GO:0140223	general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation.	A molecular function that contributes to transcription start site selection and transcription initiation. General transcription factors assemble with the RNA polymerase at promoter DNA to form the pre-initiation complex (PIC), bind to and open promoter DNA, initiate RNA synthesis and stimulate the escape of the polymerase from the promoter. Not all subunits of the general transcription factor are necessarily present at all promoters to initiate transcription. The distinction between general transcription factors and DNA-binding transcription factors is that the latter modulate the selection of which genes are expressed under specific conditions, while general transcription factors are the constitutive machinery required for transcription initiation.	Usage guidance: The distinction between general transcription factors and DNA-binding transcription factors is that the latter modulate the selection of which genes are expressed under specific conditions, while general transcription factors are the constitutive machinery required for transcription initiation. In prokaryotes, the alpha and sigma subunits of the RNA polymerase holoenzyme bind cis-regulatory DNA sequences and thus fulfil the function of dbTF, GTF and RNA polymerase all-in-one.
GO:0001181	RNA polymerase I general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase I. Factors required for RNA polymerase I transcription initiation include upstream activation factor (UAF), core factor (CF), TATA binding protein (TBP) and RRN3.	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase I. Factors required for RNA polymerase I transcription initiation include upstream activation factor (UAF), core factor (CF), TATA binding protein (TBP) and RRN3. RNA polymerase I transcribes the three largest rRNAs, 5.8S, 18S, and 28S.
GO:0016251	RNA polymerase II general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase II. The general transcription factors for RNA polymerase II include TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TATA-binding protein (TBP).	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase II. The general transcription factors for RNA polymerase II include TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TATA-binding protein (TBP). RNA polymerase II transcribes all messenger RNAs (mRNAs) and most regulatory, untranslated RNAs.
GO:0000995	RNA polymerase III general transcription initiation factor activity	An activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase III. Factors required for RNA polymerase III transcription initiation include TFIIIA, TFIIIB and TFIIIC.	A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase III. Factors required for RNA polymerase III transcription initiation include TFIIIA, TFIIIB and TFIIIC. A general transcription initiation factor activity that contributes to transcription start site selection and transcription initiation of genes transcribed by RNA polymerase III. Factors required for RNA polymerase III transcription initiation include TFIIIA, TFIIIB and TFIIIC. RNA polymerase III transcribes genes encoding short RNAs, including tRNAs, 5S rRNA, U6 snRNA, the short ncRNA component of RNases P, the mitochondrial RNA processing (MRP) RNA, the signal recognition particle SRP RNA, and in higher eukaryotes a number of micro and other small RNAs.
xxxxxx	xxxxxx	xxxxxx	xxxxxx	xxxxxx
GO:0140416	transcription regulator inhibitor activity	An activity that stops, prevents, or reduces the activity of a DNA binding transcription factor activity.	A molecular function regulator that inhibits the activity of a transcription regulator via direct binding and/or post-translational modification.	Usage guidance: transcription regulator inhibitors bind to a transcription regulator to prevent it from reaching the chromatin. This activity does not occur at the promoter. For activities that do occur at the promoter, consider GO:0001217 ; DNA-binding transcription repressor activity or GO:0003714 ; transcription corepressor activity. An example of a transcription regulator is TCF23 Q7RTU1 is an example of a protein that regulates transcription factors by heterodimerising or binding to DbTFs and prevent DNA binding and their specific genomic binding site where the dbTF would have activated or repressed transcription. Also an example is NFKBIA P25963 which has a different way of regulating transcription factor activity by sequestering the dbTF (complex) in the cytoplasm. Another example is the HSP90 and HSP23 proteins that sequester steroid receptors away from the DNA.
GO:0140537	transcription regulator activator activity	NEW	A molecular function regulator that increases the activity of a transcription regulator via direct binding and/or post-translational modification.	Usage guidance: transcription regulator activators bind to a transcription regulator to allow it to reach the chromatin or to contact other transcriptional regulators. This activity does not occur at the promoter. For activities that do occur at the promoter, consider GO:0001216 ; DNA-binding transcription activator activity or GO:0003713; transcription coactivator activity; those activities respectively bind DNA themselves or positively regulate a transcription regulator when it is located at the chromatin.
xxxxxx	xxxxxx	xxxxxx	xxxxxx	xxxxxx
GO:0001070	RNA-binding transcription regulator activity	Interacting selectively and non-covalently with an RNA sequence in order to modulate transcription. This function is known to occur in phages and viruses, for example the lambda N and the HIV tat proteins are necessary to allow RNA polymerase to read through terminator sequences.	A transcription regulator activity that modulates the transcription of specific gene sets via selective and non-covalent binding to a specific RNA sequence. This function is known to occur in phages and viruses, for example the lambda N and the HIV tat proteins are necessary to allow RNA polymerase to read through terminator sequences.
GO:0003711	transcription elongation regulator activity	A molecular function that regulates transcriptional elongation by enabling the transition from transcription initiation to elongation or by altering the elongation properties of the enzyme during the elongation phase of transcription.	OK

[pgaudet]

I made the changes shown above but of course more changes can be made.

[pgaudet]

Note on GTFs:

1. GTF definition

• GTF proposed definition (yesterday): A molecular function that contributes to transcription start site selection and transcription initiation.
• comment: General transcription factors assemble with the RNA polymerase at promoter DNA to form the pre-initiation complex (PIC), bind to and open promoter DNA, initiate RNA synthesis and stimulate the escape of the polymerase from the promoter. Not all subunits of the general transcription factor are necessarily present at all promoters to initiate transcription. The distinction between general transcription factors and DNA-binding transcription factors is that the latter modulate the selection of which genes are expressed under specific conditions, while general transcription factors are the constitutive machinery required for transcription initiation. In prokaryotes, the alpha and sigma subunits of the RNA polymerase holoenzyme bind cis-regulatory DNA sequences and thus fulfil the function of dbTF, GTF and RNA polymerase all-in-one.
• GTF new proposal (based on Paul’s feedback): A molecular function required for core promoter activity that mediates the assembly of the RNA polymerase holoenzyme at promoter DNA to form the pre-initiation complex (PIC). General transcription factors (GTFs) bind to and open promoter DNA, initiate RNA synthesis and stimulate the escape of the polymerase from the promoter. Not all subunits of the general transcription factor are necessarily present at all promoters to initiate transcription. GTFs act at each promoter, although the exact subunit composition at individual promoters may vary.

2. Clarification on bacterial GTFs

We have this in the comment: In prokaryotes, the alpha and sigma subunits of the RNA polymerase holoenzyme bind cis-regulatory DNA sequences and thus fulfil the function of dbTF, GTF and RNA polymerase all-in-one.

This is confusing because we say that GTFs do not provide specificity. Does that mean that that bacteria do not have GTFs ? Speficially, how should the gene products be annotated ?

• RNA polymerase = RNA polymerase activity (not a transcription regulator)
• alpha subunit
• sigma sigma subunit = dbTF ? GTF ? do we need a different function ?

Note that we do have ‘sigma factor activity’ function, defined as "Sigma factors act as the promoter specificity subunit of eubacterial and plant plastid multisubunit RNA polymerases, whose core subunit composition is often described as alpha(2)-beta-beta-prime. Although sigma does not bind DNA on its own, when combined with the core to form the holoenzyme, the sigma factor binds specifically to promoter elements. The sigma subunit is released once elongation begins.”

• 'sigma factor activity' is directly under ‘transcription regulator activity’
• is it possible that there is no bacterial GTF ? I dont find any annotations. I think archae have them, not eubacteria ?

@colinlog replied

Yes, no GTF in bacteria but Sigma instead with its nice current definition. That sounds very nice to me! I guess archea are like eukaryotes, but no need to comment on that...

[krchristie]

There is some variability across species about exactly which polymerases transcribe what, which is the list of what is transcribed by each RNAP was removed some time ago. If we are going to include this type of information, it should be done in a less concrete way to accomodate that variability.

RNA polymerase III transcribes genes encoding short RNAs, including tRNAs, 5S rRNA, U6 snRNA, the short ncRNA component of RNases P, the mitochondrial RNA processing (MRP) RNA, the signal recognition particle SRP RNA, and in higher eukaryotes a number of micro and other small RNAs.

• Def xref: PMID:27068803, PMID:20413673

RNA polymerase III transcribes genes encoding short RNAs, generally including all tRNAs, the 5S rRNA, the U6 snRNA, and often including the short ncRNA component of RNases P, the mitochondrial RNA processing (MRP) RNA, the signal recognition particle SRP RNA, as well as a number of other micro and small RNAs, though there is some variability across species as to whether a given small noncoding RNA is transcribed by RNA polymerase II or RNA polymerase III.

add: PMID: 17977614

Similarly for RNA pol I and pol II

GO:0001181 RNA polymerase I general transcription initiation factor activity

* Add to the definition: RNA polymerase I transcribes the three largest rRNAs, 5.8S, 18S, and 28S.

* Add Def xref:PMID: 31358304, PMID: 25346433

I would definitely NOT list the sizes of the rRNAs so concretely as they are not conserved across all taxa, nor are they transcribed separately as this implies.

In all species characterized, RNA polymerase I transcribes a large polycistronic transcript that is processed into several mature rRNAs (3 or 4 depending on the species), including the large subunit rRNA (28S in humans), the small subunit rRNA (18S in humans), as well as one or two additional smaller rRNAs (the 5.8S rRNA in humans). In most species, this large rRNA transcript is the sole product of RNA polymerase I. However there are rare exceptions, such as Trypanosoma brucei, where RNA polymerase I also transcribes certain mRNAs.

add: PMID: 17972917,

GO:0016251 RNA polymerase II general transcription initiation factor activity

• Add to the definition: RNA polymerase II transcribes all messenger RNAs (mRNAs) and most regulatory, untranslated RNAs.
  • Def xref: PMID: 23442138

In most species, RNA polymerase II transcribes all messenger RNAs (mRNAs), most untranslated regulatory RNAs, the majority of the snoRNAs, four of the five snRNAs (U1, U2, U4, and U5), and other small noncoding RNAs. For some small RNAs there is variability between species as to whether it is transcribed by RNA polymerase II or RNA polymerase III. However there are also rare exceptions, such as Trypanosoma brucei, where RNA polymerase I transcribes certain mRNAs in addition to its normal role in rRNA transcription.

add: PMID: 10747032

[pgaudet]

Thanks @krchristie , I made the changes you suggested.