New term request: Chromatin modifier-associated region identification by ChIP-Seq assay

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568
Synonyms: chromatin modifier binding site identification by ChIP-Seq assay
Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase.
Definition source: PMID 19212405
Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent.
Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue"
Editors: Paul D. Thomas, Yang Chai

Reported by: thomaspd1

Original Ticket: obi/obi-terms/782

Thanks for submitting. We plan to start working on them and hope to be back in touch soon. If you are available for the Oct. 12 obi-dev call we can discuss then.

Original comment by: cstoeckert

EP300 is also a transcription factor (GO:0001102 as listed on http://www.ncbi.nlm.nih.gov/gene/328572. Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.

Original comment by: cstoeckert

An example of a chromatin modifier that is not a transcription factor would be sometime that modifies histones such as a histone deacetylase.

Original comment by: alanruttenberg

An example of a chromatin modifier that is not a transcription factor would be sometime that modifies histones such as a histone deacetylase. On Mon, Oct 12, 2015 at 12:25 PM Chris Stoeckert stoeckert@users.sf.net wrote:

EP300 is also a transcription factor (GO:0001102 as listed on http://www.ncbi.nlm.nih.gov/gene/328572. Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.

[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay*

Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas

Last Updated: Mon Oct 05, 2015 04:59 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568

Synonyms: chromatin modifier binding site identification by ChIP-Seq assay

Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase.

Definition source: PMID 19212405

Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent.

Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue"

Editors: Paul D. Thomas, Yang Chai

Sent from sourceforge.net because you indicated interest in https://sourceforge.net/p/obi/obi-terms/782/

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Original comment by: alanruttenberg

Sorry but histone deacetylase is a functional class and not an example. Hdac1 is a histone deacetylase that is also annotated as a transcription factor (http://www.ncbi.nlm.nih.gov/gene/433759). I guess I should have just said that my understanding is that all chromatin modifiers that one would ChIP-seq to find their binding site are transcription factors.

The ENCODE listing at UCSC has a matrix of ChIP-seq with just two categories: Histone Modification and Transcription Factor (https://genome.ucsc.edu/ENCODE/dataMatrix/encodeChipMatrixHuman.html) where EP300 and HDAC1 are listed under Transcription Factor. To me this reflects the common usage and expectation for where to find these chromatin modifiers. If FaceBase needs a further specification of ChIP-seq of chromatin modifiers then we should have a subtype of "transcription factor binding site identification by ChIP-Seq assay” rather than a sibling class to avoid EP300 ChiP-seq being inconsistently assigned to one or the other.

Chris

On Oct 12, 2015, at 2:40 PM, Alan Ruttenberg alanr@users.sf.net wrote:

An example of a chromatin modifier that is not a transcription factor would be sometime that modifies histones such as a histone deacetylase. On Mon, Oct 12, 2015 at 12:25 PM Chris Stoeckert stoeckert@users.sf.net mailto:stoeckert@users.sf.net wrote:

EP300 is also a transcription factor (GO:0001102 as listed on http://www.ncbi.nlm.nih.gov/gene/328572. http://www.ncbi.nlm.nih.gov/gene/328572. Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.

[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay* Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas

Last Updated: Mon Oct 05, 2015 04:59 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai Sent from sourceforge.net because you indicated interest in https://sourceforge.net/p/obi/obi-terms/782/ https://sourceforge.net/p/obi/obi-terms/782/ To unsubscribe from further messages, please visit https://sourceforge.net/auth/subscriptions/ https://sourceforge.net/auth/subscriptions/ [obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay

Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas Last Updated: Mon Oct 12, 2015 06:23 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai Sent from sourceforge.net because you indicated interest in https://sourceforge.net/p/obi/obi-terms/782/ https://sourceforge.net/p/obi/obi-terms/782/ To unsubscribe from further messages, please visit https://sourceforge.net/auth/subscriptions/ https://sourceforge.net/auth/subscriptions/

Original comment by: cstoeckert

Just to be clear, no intent to argue other than to undersand what the answer to issue might be, which I found intriguing, particularly after your response, Chris.

On Mon, Oct 12, 2015 at 4:04 PM Chris Stoeckert stoeckert@users.sf.net wrote:

Sorry but histone deacetylase is a functional class and not an example. Hdac1 is a histone deacetylase that is also annotated as a transcription factor

It was shorthand to say that there is nothing in the definition of a histone deacetylase that necessitates that it have transcription factor activity. It's also the case that many proteins have more than one function, so it is not surprising that some HDACs can be TFs. In GO, histone deacetylase activity is not a subclass of the TF-related classes (see below).

(http://www.ncbi.nlm.nih.gov/gene/433759). I guess I should have just said that my understanding is that all chromatin modifiers that one would ChIP-seq to find their binding site are transcription factors.

Not sure. It is the job of the histones to interact with DNA in that they form structures around which DNA wraps. Here is an article in which the two activities - histone binding versus transcription factor are distinguished:

Identifying Differential Histone Modification Sites from ChIP‐seq Data http://goo.gl/BW7LFP

"Regions with enriched number of ChIP fragments are potential histone modification sites or transcription factor binding sites"

My earlier understanding of TFs have them binding upstream of the coding region and functioning in the process of eventually recruiting polymerase. In this paper they describe the histone acting in a coding region.

KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation http://www.pnas.org/content/107/21/9671.full

Part of the problem is with the term "transcription factor". GO doesn't have a single term for transcription factor.

[Current term] GO:1903506 regulation of nucleic acid-templated transcription [is_a relation] GO:1903507 negative regulation of nucleic acid-templated transcription [is_a relation] GO:1903508 positive regulation of nucleic acid-templated transcription [is_a relation] GO:1900259 regulation of RNA-directed RNA polymerase activity [is_a relation] GO:0006355 regulation of transcription, DNA-templated [part_of relation] GO:0000990 transcription factor activity, core RNA polymerase binding [part_of relation] GO:0000988 transcription factor activity, protein binding

Reading the two TF Activity definitions, both say that DNA binding isn't even a necessary condition for having TF activity. The closest to what I understand as TF is GO:0000990.

The ENCODE listing at UCSC has a matrix of ChIP-seq with just two

categories: Histone Modification and Transcription Factor ( https://genome.ucsc.edu/ENCODE/dataMatrix/encodeChipMatrixHuman.html) where EP300 and HDAC1 are listed under Transcription Factor. To me this reflects the common usage and expectation for where to find these chromatin modifiers.

It looks to me that the distinction they are making is between antibodies to post-translationally modified histones versus non-modification-specific DNA binding proteins. I looked a bit to find out what ENCODE means by transcription factor. Here's one definition they give:

"Transcription factors (TFs) are proteins that bind to DNA and interact with RNA polymerases to regulate gene expression. Some TFs contain a DNA binding domain and can bind directly to specific short DNA sequences ('motifs'); others bind to DNA indirectly through interactions with TFs containing a DNA binding domain. High-throughput antibody capture and sequencing methods (e.g. chromatin immunoprecipitation followed by sequencing, or 'ChIP-seq') can be used to identify regions of TF binding genome-wide. These regions are commonly called ChIP-seq peaks."

If FaceBase needs a further specification of ChIP-seq of chromatin modifiers then we should have a subtype of "transcription factor binding site identification by ChIP-Seq assay” rather than a sibling class to avoid EP300 ChiP-seq being inconsistently assigned to one or the other.

It seems to me that if their intention is to find transcription factor binding sites it's a different assay than if the intention is to find histone modifications. I believe different analyses can be used in TF versus Histone experiments with Chip-Seq. For example, this one: Identifying differential histone modification sites from ChIP-seq data http://www.ncbi.nlm.nih.gov/pubmed/22130888.

A last thought: AFAIK it isn't necessarily the case that the site where a histone binds when acting as a transcription factor (when it has such activity) is the same as where it binds as a structural element of a nucleosome.

Maybe the issue should be punted to GO.

Later, Alan

Chris

On Oct 12, 2015, at 2:40 PM, Alan Ruttenberg alanr@users.sf.net wrote:

An example of a chromatin modifier that is not a transcription factor would be sometime that modifies histones such as a histone deacetylase.

On Mon, Oct 12, 2015 at 12:25 PM Chris Stoeckert stoeckert@users.sf.net stoeckert@users.sf.net wrote:

EP300 is also a transcription factor (GO:0001102 as listed on

http://www.ncbi.nlm.nih.gov/gene/328572. http://www.ncbi.nlm.nih.gov/gene/328572.

Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.

[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ New term

request: Chromatin modifier-associated region identification by ChIP-Seq assay* Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas

Last Updated: Mon Oct 05, 2015 04:59 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai

Sent from sourceforge.net because you indicated interest in

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Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas Last Updated: Mon Oct 12, 2015 06:23 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai

Sent from sourceforge.net because you indicated interest in https://sourceforge.net/p/obi/obi-terms/782/ https://sourceforge.net/p/obi/obi-terms/782/ To unsubscribe from further messages, please visit https://sourceforge.net/auth/subscriptions/ https://sourceforge.net/auth/subscriptions/

[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay*

Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas Last Updated: Mon Oct 12, 2015 06:23 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568

Synonyms: chromatin modifier binding site identification by ChIP-Seq assay

Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase.

Definition source: PMID 19212405

Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent.

Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue"

Editors: Paul D. Thomas, Yang Chai

Sent from sourceforge.net because you indicated interest in https://sourceforge.net/p/obi/obi-terms/782/

To unsubscribe from further messages, please visit https://sourceforge.net/auth/subscriptions/

Original comment by: alanruttenberg

Enjoy Italy!!

edit(underlined): It seems to me that if their intention is to find transcription factor binding sites it's a different assay than if the intention is to find regions where histone modifiers do their work. I believe different analyses can be used in TF versus Histone experiments with Chip-Seq. For example, this one: Identifying differential histone modification sites from ChIP-seq data http://www.ncbi.nlm.nih.gov/pubmed/22130888.

I was looking at the OBI hierarchy. Perhaps the definition for chip-Seq is too tight: an assay which aims at identifying protein binding sites in genomic DNA and determining how protein may regulate gene transcription by relying on immunoprecipitation of DNA bound protein, creation of a library of corresponding DNA fragments (either single or paired-end fragments) and subsequent sequencing using parallelized sequencing methods.

The underlined: and determining how protein may regulate gene transcription is the part I think might be worth dropping(or making a subclass). It seems there are a number of goals that ChIP-seq the method is uses, not all of which are to directly study gene regulation (i.e. the specified output is not information about gene expression). A study of epigenetics could use ChIP-seq to look at issue of inheritence.

So in this paper Epigenetic inheritance uncoupled from sequence-specific recruitment https://www.sciencemag.org/content/348/6230/1258699.full.pdf they used the CHiP-seq as a probe for the existence of the histone modifications in a target region (presumably using antibodies to the modified histones as pull down). They use a reporter assay to check for the bases that are modified by them (silencing it). They want to show that just having the modified histones present is enough to maintain the DNA modifications in place. They show that DNA modification can be established by binding of a 'starter sequence', but that the starter sequence binding can be removed and the DNA modifications can persist. They also show a particular domain in the modified histones isn't necessary to get the modifications established. Then they show that the domain on the histones (clr4) is required for the silencing to be maintained, as investigate other proteins that contribute to maintenance.

So this assay would be something close to histone modification identification by ChIP-Seq assay, different in that the goal isn't to discover where the modified histones are but rather to check whether a specific set of modified histones are in a specified region.

Returning to the request term, after doing yet more poking it looks to me that while the assay, on the surface, looks like a standard dna binding assay for EP300, EP300 is classified as a transcriptional coactivator. So I'm not sure whether the DNA sequenced in the CHiP-seq experiment was bound to EP300 or to a transcription factor that EP300 binds to. I think it is the latter, but other opinions would be welcome.

Given that I'll go out on a limb (again) and say this assay isn't a 'A ChIP-seq assay to identify binding sites for transcription factors'. OTOH, what's done isn't specific to the function "chromatin modification". Rather it's a CHiP-seq assay for transcriptional cofactors - i.e. something that binds to protein that actually binds DNA. Presumably it was determined elsewhere that EP300 doesn't bind DNA (being a cofactor). In GO it is annotated with 'regulation of transcription, DNA-templated http://amigo.geneontology.org/amigo/term/GO:0006355', but not translation regulator activity, nucleic acid binding http://amigo.geneontology.org/amigo/term/GO:0090079

One version of a revised hierarchy:

ChIP-seq assay

chromatin immunoprecipitation with exonuclease sequencing assay (seems like this should be a defined class as it could be super to any of the below)
histone modification identification by ChIP-Seq assay (we know the modifications in advance) -- histone modification presence in region by ChIP-Seq assay (we know the modifications and the region in advance)
transcription factor binding site identification by ChIP-Seq assay (we know the TF in advance)
transcription cofactor activity region identification (We may not know the TF at all) -- Chromatin modifier-associated activity region identification (the requested assay type, cofactor specialized to Chromatin modifier)

Alan

On Mon, Oct 12, 2015 at 6:10 PM Alan Ruttenberg alanruttenberg@gmail.com wrote:

Just to be clear, no intent to argue other than to undersand what the answer to issue might be, which I found intriguing, particularly after your response, Chris.

On Mon, Oct 12, 2015 at 4:04 PM Chris Stoeckert stoeckert@users.sf.net wrote:

Sorry but histone deacetylase is a functional class and not an example. Hdac1 is a histone deacetylase that is also annotated as a transcription factor

It was shorthand to say that there is nothing in the definition of a histone deacetylase that necessitates that it have transcription factor activity. It's also the case that many proteins have more than one function, so it is not surprising that some HDACs can be TFs. In GO, histone deacetylase activity is not a subclass of the TF-related classes (see below).

(http://www.ncbi.nlm.nih.gov/gene/433759). I guess I should have just said that my understanding is that all chromatin modifiers that one would ChIP-seq to find their binding site are transcription factors.

Not sure. It is the job of the histones to interact with DNA in that they form structures around which DNA wraps. Here is an article in which the two activities - histone binding versus transcription factor are distinguished:

Identifying Differential Histone Modification Sites from ChIP‐seq Data http://goo.gl/BW7LFP

"Regions with enriched number of ChIP fragments are potential histone modification sites or transcription factor binding sites"

My earlier understanding of TFs have them binding upstream of the coding region and functioning in the process of eventually recruiting polymerase. In this paper they describe the histone acting in a coding region.

KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation http://www.pnas.org/content/107/21/9671.full

Part of the problem is with the term "transcription factor". GO doesn't have a single term for transcription factor.

[Current term] GO:1903506 regulation of nucleic acid-templated transcription [is_a relation] GO:1903507 negative regulation of nucleic acid-templated transcription [is_a relation] GO:1903508 positive regulation of nucleic acid-templated transcription [is_a relation] GO:1900259 regulation of RNA-directed RNA polymerase activity [is_a relation] GO:0006355 regulation of transcription, DNA-templated [part_of relation] GO:0000990 transcription factor activity, core RNA polymerase binding [part_of relation] GO:0000988 transcription factor activity, protein binding

Reading the two TF Activity definitions, both say that DNA binding isn't even a necessary condition for having TF activity. The closest to what I understand as TF is GO:0000990.

The ENCODE listing at UCSC has a matrix of ChIP-seq with just two

categories: Histone Modification and Transcription Factor ( https://genome.ucsc.edu/ENCODE/dataMatrix/encodeChipMatrixHuman.html) where EP300 and HDAC1 are listed under Transcription Factor. To me this reflects the common usage and expectation for where to find these chromatin modifiers.

It looks to me that the distinction they are making is between antibodies to post-translationally modified histones versus non-modification-specific DNA binding proteins. I looked a bit to find out what ENCODE means by transcription factor. Here's one definition they give:

"Transcription factors (TFs) are proteins that bind to DNA and interact with RNA polymerases to regulate gene expression. Some TFs contain a DNA binding domain and can bind directly to specific short DNA sequences ('motifs'); others bind to DNA indirectly through interactions with TFs containing a DNA binding domain. High-throughput antibody capture and sequencing methods (e.g. chromatin immunoprecipitation followed by sequencing, or 'ChIP-seq') can be used to identify regions of TF binding genome-wide. These regions are commonly called ChIP-seq peaks."

If FaceBase needs a further specification of ChIP-seq of chromatin modifiers then we should have a subtype of "transcription factor binding site identification by ChIP-Seq assay” rather than a sibling class to avoid EP300 ChiP-seq being inconsistently assigned to one or the other.

It seems to me that if their intention is to find transcription factor binding sites it's a different assay than if the intention is to find histone modifications. I believe different analyses can be used in TF versus Histone experiments with Chip-Seq. For example, this one: Identifying differential histone modification sites from ChIP-seq data http://www.ncbi.nlm.nih.gov/pubmed/22130888.

A last thought: AFAIK it isn't necessarily the case that the site where a histone binds when acting as a transcription factor (when it has such activity) is the same as where it binds as a structural element of a nucleosome.

Maybe the issue should be punted to GO.

Later, Alan

Chris

On Oct 12, 2015, at 2:40 PM, Alan Ruttenberg alanr@users.sf.net wrote:

An example of a chromatin modifier that is not a transcription factor would be sometime that modifies histones such as a histone deacetylase.

On Mon, Oct 12, 2015 at 12:25 PM Chris Stoeckert stoeckert@users.sf.net stoeckert@users.sf.net wrote:

EP300 is also a transcription factor (GO:0001102 as listed on

http://www.ncbi.nlm.nih.gov/gene/328572. http://www.ncbi.nlm.nih.gov/gene/328572.

Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.

[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ New term

request: Chromatin modifier-associated region identification by ChIP-Seq assay* Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas

Last Updated: Mon Oct 05, 2015 04:59 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai

Sent from sourceforge.net because you indicated interest in

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https://sourceforge.net/auth/subscriptions/ https://sourceforge.net/auth/subscriptions/ [obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay

Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas Last Updated: Mon Oct 12, 2015 06:23 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568 Synonyms: chromatin modifier binding site identification by ChIP-Seq assay Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase. Definition source: PMID 19212405 Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent. Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue" Editors: Paul D. Thomas, Yang Chai

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[obi-terms:#782] http://sourceforge.net/p/obi/obi-terms/782/ New term request: Chromatin modifier-associated region identification by ChIP-Seq assay*

Status: open Group: general Created: Fri Oct 02, 2015 12:34 AM UTC by Paul Thomas Last Updated: Mon Oct 12, 2015 06:23 PM UTC Owner: nobody

I'm trying to get new terms to describe some of the data in the FaceBase resource (this project is funded by NIH/NIDCR, website at facebase.org).

Suggested term name: Chromatin modifier-associated region identification by ChIP-Seq assay. There is currently a term for "transcription factor binding site identification by ChIP-Seq assay" so this could be added as a sibling. This is meant to cover chromatin modifiers like EP300, which is a histone acetyltransferase. So it is not a histone modification, but is the enzyme that adds a histone modification. It can refer to GO:0016568

Synonyms: chromatin modifier binding site identification by ChIP-Seq assay

Definition: A ChIP-seq assay to identify regions of chromatin bound to a chromatin modifying protein, e.g. a histone acetyltransferase.

Definition source: PMID 19212405

Parent term: suggest new term "reporter gene assay" (Definition: An assay in which expression of a reporter gene is detected that was inserted under the control of a regulatory sequence of interest.), with the existing term "Promoter activity detection by reporter gene assay" as a child of this same parent.

Example of usage: PMID 19212405: "we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue"

Editors: Paul D. Thomas, Yang Chai

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Original comment by: alanruttenberg

I like the structure Alan proposed. The essential distinction (that made me request a new term) is between a factor that directly binds to the DNA, and one that is associated with that region by binding to a protein (that either itself directly binds to DNA or to another chromatin-associated protein...). I tried to send an email early today but I don't see it in the discussion. I've pasted it in below.

Thanks, Paul.

We struggled with this in the GO as well, which is reflected in the parent term “transcription factor, protein binding” which is more properly considered to be a transcription cofactor. The most common usage of “transcription factor” refers to a DNA binding factor. EP300 does not bind DNA directly (despite the GO annotations that seem to suggest it does), and is thus more properly considered a cofactor that functions via histone acetylation.

Original comment by: thomaspd1

Given that the annotation of transcription co-factors is recognized as an issue in GO, I'm OK with the original request that the "chromatin modifier binding site identification by ChIP-Seq assay" be placed directly under ChIP-seq assay. We should add an editor's note to capture the essence of this discussion.

Original comment by: cstoeckert

Discussed on Nov. 23 call. currently have

transcription factor binding site identification by ChIP-Seq assay now propose to add as sibling. Will be a child of ChIP-Seq assay. may add a logical axiom adding an objective of identifying transcription cofactor activity region.
transcription cofactor activity region identification by ChIP-Seq assay AI: Chris will add.

obi-ontology / obi

New term request: Chromatin modifier-associated region identification by ChIP-Seq assay #765

EP300 is also a transcription factor (GO:0001102 as listed on http://www.ncbi.nlm.nih.gov/gene/328572. Are there chromatin modifiers that are not also considered transcription factors? If not it's not clear that this would be a sibling term.