Transcriptional gene silencing (TGS)

[ValWood]

I read quite a few papers today that refer to "Transcriptional gene silencing (TGS) This used to be an independent term, but it is now a synonym of heterochromatin assembly, but it seems narrower.

e.g. PMID:21211723 "Clr4 is required for both TGS and cis-PTGS of heterochromatic loci (Noma et al., 2004). Transcripts that escape heterochromatic TGS are processed into siRNAs by RNAi machinery. asf1-1 and HIRA mutants only affect TGS and not cis-PTGS. Indeed, we observed increased levels of siRNAs in asf1-1 and HIRA mutants (Figure 1E), revealing that dg/dh repeats are derepressed in these mutants but transcripts are not accumulating due to their degradation by RNAi."

is this synonym on the correct term, is there another term that I should be using? it's definitely narrower than "heterochromatin assembly"

I'll add the other references tomorrow

v

@pgaudet @colinlog

[pgaudet]

How about 'GO:1902795 siRNA-mediated facultative heterochromatin formation'? (based on the text you cite from the intro)

However according to our documentation, hirA is rather involved in 'GO:0045815 transcriptional initiation-coupled chromatin remodeling' and 'GO:0140673 transcriptional elongation-coupled chromatin remodeling' https://docs.google.com/presentation/d/15fDBhmO54zSJms25aV5nX3kgSwsHMnWgdSuPdo-ukyw/edit#slide=id.gf4888089cb_0_0

This seems consistent with the data in Fig 5 "Asf1 and SHREC Promote Nucleosome Occupancy at Heterochromatic Loci"

[pgaudet]

@ValWood We moved away from the (P)TSG terminology because it's used inconsistently in the literature, often as a tool to silence genes experimentally. This is why it's a synonym of the very high level term 'heterochromatin formation', different papers use "TGS" for different mechanisms.

[ValWood]

In the context it is used in the heterochromatin it is used as shorthand for "heterochromatic transcriptional gene silencing"

See for example:

in review https://pubmed.ncbi.nlm.nih.gov/22243696/ Different means, same end-heterochromatin formation by RNAi and RNAi-independent RNA processing factors in fission yeast

and also review https://pubmed.ncbi.nlm.nih.gov/37207657/ The molecular basis of heterochromatin assembly and epigenetic inheritance

Also we still have GO:0016441 post-transcriptional gene silencing (PTGS)

Another issue is that with the current arrangement "heterochromatin assembly" is a descendant of "gene expression", but heterochromatin assembly at the centromere isn't regulating gene expression.

Perhaps heterochromatic gene silencing works better as a synonym of facultative heterochromatin formation?

But the transcriptional gene silencing seems to be more about histone deacetylation and nucleosome occupancy. it isn't referring to all of the heterochromatin formation machinery although they work in parallel.

I have some more papers to read today....

[ValWood]

I just read your first comment.

I sort of agree, but I feel that i) we are not able to represent the "chromatin remodelling of transcriptional repression", everything is GO:0045815 transcriptional initiation-coupled chromatin remodeling, but the repressive (deacetylation) pathway precedes heterochromatin assembly, and the remodelling for activation precedes/acts in parallel with transcription initiation. This conflates 2 important types of chromatin remodelling pathway.

ii) the syonym "transcriptional gene silencing/post transcriptional gene silencing" is on the wrong term

[ValWood]

Re However according to our documentation, hirA is rather involved in 'GO:0045815 transcriptional initiation-coupled chromatin remodeling' and 'GO:0140673 transcriptional elongation-coupled chromatin remodeling'

HIRA is involved in silencing heterochromatic loci (Greenall et al., 2006; Kaufman et al., 1998; Sharp et al., 2001; Ye et al., 2007).

[ValWood]

Seems to be about promoting nucleosome occupancy

[ValWood]

This paper also implies quite a difference: [PMID:21211723] Clr4 is required for both TGS and cis-PTGS of heterochromatic loci (Noma et al., 2004). Transcripts that escape heterochromatic TGS are processed into siRNAs by RNAi machinery. asf1-1 and HIRA mutants only affect TGS and not cis-PTGS.

The model:

[colinlog]

Dear Val and Pascale, I will get back to you both by the end of the weekend when I'll have read the papers and other relevant literature in detail.. Essentially, it appears to me that the molecular phenotypes described in these papers intersect with failing cellular mechanisms to cope with transcripts emanating from cryptic (not selected for by evolation) RNA polymerase II transcription initiation sites that are revealed when nucleosome / chromatin assembly fails. However there is more to this, I believe the results also touch on the idea that heterochromatin machinery is not only transcription repressive, but, under some conditions, at some types of gene promoters it actually activates transcription. Best, Colin .

On Wed, Jan 17, 2024 at 7:02 AM pgaudet @.***> wrote:

How about 'GO:1902795 siRNA-mediated facultative heterochromatin formation'?

However according to our documentation, hirA is rather involved in 'GO:0045815 transcriptional initiation-coupled chromatin remodeling' and 'GO:0140673 transcriptional elongation-coupled chromatin remodeling'

https://docs.google.com/presentation/d/15fDBhmO54zSJms25aV5nX3kgSwsHMnWgdSuPdo-ukyw/edit#slide=id.gf4888089cb_0_0

— Reply to this email directly, view it on GitHub https://github.com/geneontology/go-ontology/issues/26804#issuecomment-1894992749, or unsubscribe https://github.com/notifications/unsubscribe-auth/ALZVLKCC4X3RAZMEGERBAEDYO5SONAVCNFSM6AAAAABB5KT7W6VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTQOJUHE4TENZUHE . You are receiving this because you were mentioned.Message ID: @.***>

[ValWood]

On 18/01/2024 10:44, colinlog wrote:

Dear Val and Pascale, I will get back to you both by the end of the weekend when I'll have read the papers and other relevant literature in detail.. Essentially, it appears to me that the molecular phenotypes described in these papers intersect with failing cellular mechanisms to cope with transcripts emanating from cryptic (not selected for by evolation) RNA polymerase II transcription initiation sites that are revealed when nucleosome / chromatin assembly fails.

Hi Colin,

I think you are right here. I have been reading chromatin appears all week and it's so complicated!

RE TGS, I think now that this is 2 things,  it is really broader then heterochromatin assembly (heterochromatin assembly plus degradation), and I think you are correct about the cryptic transcripts but I'm finding it all difficult to  separate all of the different pathways.

For the pathway described as TGS this is useful https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035992/

Re the surveillance machinery I read a paper https://europepmc.org/article/MED/21892171 which showed that deletion of RNA surveillance  component Mlo3 (S.c YRA1) can partially rescue  deletion of essential RNAi components dcr1delta - but presumably this is  just somehow bypassing  the RNAi pathway ... I can't figure out how !

However there is more to this, I believe the results also touch on the idea that heterochromatin machinery is not only transcription repressive, but, under some conditions, at some types of gene promoters it actually activates transcription.

Well transcription is required for heterochromatin assembly (which presumably occurs in S-phase to establish the heterochromatin?)

There are so many considerations I just can't work out how everything fits together in a universal model....

I hope you can enlighten!

Val

Best, Colin .

On Wed, Jan 17, 2024 at 7:02 AM pgaudet @.***> wrote:

How about 'GO:1902795 siRNA-mediated facultative heterochromatin formation'?

However according to our documentation, hirA is rather involved in 'GO:0045815 transcriptional initiation-coupled chromatin remodeling' and 'GO:0140673 transcriptional elongation-coupled chromatin remodeling'

https://docs.google.com/presentation/d/15fDBhmO54zSJms25aV5nX3kgSwsHMnWgdSuPdo-ukyw/edit#slide=id.gf4888089cb_0_0

— Reply to this email directly, view it on GitHub

https://github.com/geneontology/go-ontology/issues/26804#issuecomment-1894992749, or unsubscribe

https://github.com/notifications/unsubscribe-auth/ALZVLKCC4X3RAZMEGERBAEDYO5SONAVCNFSM6AAAAABB5KT7W6VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTQOJUHE4TENZUHE . You are receiving this because you were mentioned.Message ID: @.***>

— Reply to this email directly, view it on GitHub https://github.com/geneontology/go-ontology/issues/26804#issuecomment-1898231601, or unsubscribe https://github.com/notifications/unsubscribe-auth/ABYEWKGRTQLP44SJLWSQBVDYPD4HTAVCNFSM6AAAAABB5KT7W6VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTQOJYGIZTCNRQGE. You are receiving this because you were mentioned.Message ID: @.***>

--------------aK0vZdAJmaSXlIpfmJRNKw0M Content-Type: text/html; charset=UTF-8 Content-Transfer-Encoding: 8bit

On 18/01/2024 10:44, colinlog wrote:

Dear Val and Pascale,
I will get back to you both by the end of the weekend when I'll have read
the papers and other relevant literature in detail..
Essentially, it appears to me that the molecular phenotypes described in
these papers intersect with failing cellular mechanisms to cope with
transcripts emanating from cryptic (not selected for by evolation) RNA
polymerase II transcription initiation sites that are revealed when
nucleosome / chromatin assembly fails.

Hi Colin,

I think you are right here. I have been reading chromatin appears all week and it's so complicated!

RE TGS, I think now that this is 2 things,  it is really broader then heterochromatin assembly (heterochromatin assembly plus degradation), and I think you are correct about the cryptic transcripts but I'm finding it all difficult to  separate all of the different pathways.

For the pathway described as TGS this is useful https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035992/

Re the surveillance machinery I read a paper https://europepmc.org/article/MED/21892171 which showed that deletion of RNA surveillance  component Mlo3 (S.c YRA1) can partially rescue  deletion of essential RNAi components dcr1delta - but presumably this is  just somehow bypassing  the RNAi pathway ... I can't figure out how !

However there is more to this, I believe the results also touch on the idea
that heterochromatin machinery is not only transcription repressive, but,
under some conditions, at some types of gene promoters it actually
activates transcription.

Well transcription is required for heterochromatin assembly (which presumably occurs in S-phase to establish the heterochromatin?)

There are so many considerations I just can't work out how everything fits together in a universal model....

I hope you can enlighten!

Val

Best, Colin
.

On Wed, Jan 17, 2024 at 7:02 AM pgaudet ***@***.***> wrote:

> How about 'GO:1902795 siRNA-mediated facultative heterochromatin
> formation'?
>
> However according to our documentation, hirA is rather involved in
> 'GO:0045815 transcriptional initiation-coupled chromatin remodeling' and
> 'GO:0140673 transcriptional elongation-coupled chromatin remodeling'
>
> https://docs.google.com/presentation/d/15fDBhmO54zSJms25aV5nX3kgSwsHMnWgdSuPdo-ukyw/edit#slide=id.gf4888089cb_0_0
>
> —
> Reply to this email directly, view it on GitHub
> <https://github.com/geneontology/go-ontology/issues/26804#issuecomment-1894992749>,
> or unsubscribe
> <https://github.com/notifications/unsubscribe-auth/ALZVLKCC4X3RAZMEGERBAEDYO5SONAVCNFSM6AAAAABB5KT7W6VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTQOJUHE4TENZUHE>
> .
> You are receiving this because you were mentioned.Message ID:
> ***@***.***>
>

—
Reply to this email directly, view it on GitHub, or unsubscribe.
You are receiving this because you were mentioned.Message ID: <geneontology/go-ontology/issues/26804/1898231601@github.com>

--------------aK0vZdAJmaSXlIpfmJRNKw0M--

[colinlog]

Dear Val, I am afraid I have not been gotten to this during the weekend because I am still not done grading 20 x 175 exam questions and nor reviewing 16 large grants for the Dutch research organisation, writing the book chater that I promised a close colleague to have written by February 1st and preparing for the management meetings I must attend sinds January 1st. May I ask therefore delay this discussion to Friday afternoon during the TXN work group session? Colin

[ValWood]

No hurry for me. I don't think you will be through this list by Friday! v