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Merge two parent terms into: GO:0060818 inactivation of paternal X chromosome by genomic imprinting #25955

Closed pgaudet closed 1 year ago

pgaudet commented 1 year ago

GO:0060818 inactivation of paternal X chromosome by genomic imprinting is the single child of GO:0060817 inactivation of paternal X chromosome, and has no annotations.

The reason for obsoletion is that there is not evidence for a pathways for inactivation of paternal X chromosome that is not genomic imprinting, so this term is redundant with its parent.

pgaudet commented 1 year ago
krchristie commented 1 year ago

Due to being confused by some of the term suggestions in the annotation review of "regulation of imprinting", I've just been going through all of the X inactivation annotations for mice, and updating to the appropriate specific term instead of the higher level term. I've also done a little reading for other species to understand taxonomic scope.

I agree that these two terms are identical, as well as a third term, for which "inactivation of paternal X chromosome by genomic imprinting" is also the only child term: ---- GO:0060817 - inactivation of paternal X chromosome ----- GO:0060818 - inactivation of paternal X chromosome by genomic imprinting

---- GO:0060819 - inactivation of X chromosome by genomic imprinting ----- GO:0060818 - inactivation of paternal X chromosome by genomic imprinting

All three of these terms refer to "X inactivation of the paternal X chromosome by genomic imprinting". When X inactivation occurs by imprinting, it always inactivates the paternal X chromosome. When the paternal X chromosome is selectively inactivated, it is always by imprinting.

"X inactivation of the paternal X chromosome by genomic imprinting" appears to be the ancestral form of x dosage compensation. It is still found in metatheria, e.g. marsupials. In eutheria, which includes mammals, this form of imprinting has largely been replaced by "random X chromosome inactivation". However, in small number of mammals, "X inactivation of the paternal X chromosome by genomic imprinting" still occurs.

Considering that numerous reviews distinguish "imprinted X inactivation" and "random X inactivation" as the two types of X dosage compensation in theria, I think that the term we should keep is "X inactivation of the paternal X chromosome by genomic imprinting" since it helps distinguish imprinted (iXCI) versus random rXCI. This most specific term is what I chose this past week when I reviewed ALL of the mouse annotations under the parent term "dosage compensation".

1: Dupont C, Gribnau J. Different flavors of X-chromosome inactivation in mammals. Curr Opin Cell Biol. 2013 Jun;25(3):314-21. doi: 10.1016/j.ceb.2013.03.001. Epub 2013 Apr 8. PMID: 23578369.

2: Blewitt ME, Gendrel AV, Pang Z, Sparrow DB, Whitelaw N, Craig JM, Apedaile A, Hilton DJ, Dunwoodie SL, Brockdorff N, Kay GF, Whitelaw E. SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet. 2008 May;40(5):663-9. doi: 10.1038/ng.142. Epub 2008 Apr 20. PMID: 18425126.

3: Ciaudo C, Bourdet A, Cohen-Tannoudji M, Dietz HC, Rougeulle C, Avner P. Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X chromosome inactivation. PLoS Genet. 2006 Jun;2(6):e94. doi: 10.1371/journal.pgen.0020094. Epub 2006 Jun 16. PMID: 16789828; PMCID: PMC1479048.

4: Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT. CTCF, a candidate trans- acting factor for X-inactivation choice. Science. 2002 Jan 11;295(5553):345-7. doi: 10.1126/science.1065982. Epub 2001 Dec 6. PMID: 11743158.

krchristie commented 1 year ago

Since merges are discouraged now, I suppose that you'll need to obsolete these two terms:

I do feel strongly that this term is the best term to keep as it is the most accurate description of the process

krchristie commented 1 year ago

Please also add this synonym:

"iXCI" as a RELATED synonym

The RELATED synonym "rXCI" should be added to this term: "random inactivation of X chromosome" (GO:0060816)

krchristie commented 1 year ago

I think it would be useful to add this info as a comment if it cannot be incorporated into the definition:

Imprinting controlled inactivation of the paternal X chromosome appears to be the ancestral form of sex chromosome inactivation in therian mammals.

In eutherian mammals, imprinted X inactivation (iXCI) has largely been replaced by random X inactivation in a process regulated by the Xist and additional ncRNA's encoded within the "choice" region of the X chromosome. In a few mammals with early zygotic genome activation, imprinted X inactivation of the paternal X chromsome occurs very early during embryonic development. Imprinted iXCI has been observed in mice, rats, and bovines, and is best studied in mice where it occurs in the 4 cell stage in mice. In epiblast cells which will become the embryo proper, the inactivated paternal X chromosome is reactivated and dosage compensation of the X chromosome is regenerated by random X inactivation in embryonic tissues. In extraembryonic tissues, the selective inactivation of the paternal chromosome remains and is essential for proper development of the placenta.

Selective inactivation of the paternal X chromosome via imprinting is the only form of X chromosome inactivation in marsupials, though the mechanism there may be significantly different as marsupials the Xist or transcript is not present on metatherian X chromosomes.

pgaudet commented 1 year ago
pgaudet commented 1 year ago

GO:0060818 inactivation of paternal X chromosome by genomic imprinting

GO:0060816 random inactivation of X chromosome

pgaudet commented 1 year ago

@krchristie Thanks for all this, it was immensely helpful.

WRT taxon constraints: feedback from @colinlog is that in marsupials indeed, the paternal X chromosome is inactivated throughout the body; however in mammals (including human) there is specific paternal X chromosome inactivation in the placenta, and random in the embryo proper. So I propose to only add the TC for only in Theria.

Also, I added the TC on the parent term GO:0009048 dosage compensation by inactivation of X chromosome

krchristie commented 1 year ago

@krchristie Thanks for all this, it was immensely helpful.

WRT taxon constraints: feedback from @colinlog is that in marsupials indeed, the paternal X chromosome is inactivated throughout the body; however in mammals (including human) there is specific paternal X chromosome inactivation in the placenta, and random in the embryo proper. So I propose to only add the TC for only in Theria.

Also, I added the TC on the parent term GO:0009048 dosage compensation by inactivation of X chromosome

We may want to check if this term "GO:0009048 dosage compensation by inactivation of X chromosome" may need to be broad enough to account for monotremata. They have multiple X and Y chromosomes and do something quite different, but I can't remember if the dosage compensation is considered to be inactivation of not.

pgaudet commented 1 year ago

Thanks @krchristie

I found this for marsupials: https://pubmed.ncbi.nlm.nih.gov/19802707/

Looks like there is X inactivation by other mechanisms (not involving XIST)

So I will change the taxon constraint of dosage compensation by inactivation of X chromosome to Amniota; does that seem OK ?

krchristie commented 1 year ago

Thanks @krchristie

I found this for marsupials: https://pubmed.ncbi.nlm.nih.gov/19802707/

Looks like there is X inactivation by other mechanisms (not involving XIST)

So I will change the taxon constraint of dosage compensation by inactivation of X chromosome to Amniota; does that seem OK ?

I don't understand how this paper suggests broadening the taxon constraint. From the abstract it says this:

This has lead to a number of important findings, among which is the absence of XIST in marsupials and monotremes, and the surprising finding that X-borne genes in platypus are subject to stochastic transcriptional inhibition rather than whole chromosome inactivation.

Marsupials do not have Xist, but as I mentioned in the comment I suggested you add to this term, they do have an imprinted mechanism of inactivation of the X chromosome as a unit, though the mechanism is not well understood. Marsupials are in the group metatheria, which with eutheria is a child of the taxon Theria.

Monotremes also don't have Xist, but according to the abstract above do not seem to have a mechanism of whole X chromosome inactivation, so it doesn't seem appropriate to broaden the taxon constraint of the term "dosage compensation by inactivation of X chromosome" in order to accomodate the taxon Monotremata since this term does not seem appropriate for what we currently know about monotremes.

P.S. I find it a bit frustrating when you ask for my opinion but don't wait a reasonable amount of time for me to even see the question before you act.

colinlog commented 1 year ago

Hello Karen and Pascale, Browsing the publications that cite https://pubmed.ncbi.nlm.nih.gov/19802707/ it came to light that PMID: 22722828 reports another non-coding RNA than Xist, it is called Rsx and has the propeorties of Xist, including X-chromosome coating and exclusive expression by females. As it was found in marsuplials from Australia and from South America this is likely ancestral to all marsupials. This ncRNA was also detected in the Koala genome published in 2018 (PMID: 29967444). Hence, although Xist is not found in marsupials, the molecular mechanism and the biological processes of X-chromosome inactivation is likely conserved and incarnated by Rsx. @pgaudet @krchristie

krchristie commented 1 year ago

Hello Karen and Pascale, Browsing the publications that cite https://pubmed.ncbi.nlm.nih.gov/19802707/ it came to light that PMID: 22722828 reports another non-coding RNA than Xist, it is called Rsx and has the propeorties of Xist, including X-chromosome coating and exclusive expression by females. As it was found in marsuplials from Australia and from South America this is likely ancestral to all marsupials. This ncRNA was also detected in the Koala genome published in 2018 (PMID: 29967444). Hence, although Xist is not found in marsupials, the molecular mechanism and the biological processes of X-chromosome inactivation is likely conserved and incarnated by Rsx. @pgaudet @krchristie

Hi @colinlog - Thanks for the interesting paper. I'll take a look tomorrow. I think we should be wary of going on just one paper though. I looked at a number of papers on marsupial X chromosome dosage compensation and one of them specifically talked about how inactivation of a number of different X-linked genes had been studied in various marsupials and that the studies did not yet allow one to draw conclusions about a general mechanism. I looked through my notes but am not sure what paper that was. However, in light of the fact that I don't think GO is currently annotating any marsupial species, I came to the conclusion that the existing term is probably broad enough and that there was not yet a good case for me to spend any more time reading about this topic in marsupials to make a term that is specific for the marsupial form of "X inactivation of paternal chromosome by imprinting". It seemed to me that further refinement could await greater need to annotate marsupials and greater understanding of the mechanism.

krchristie commented 1 year ago

@krchristie Thanks for all this, it was immensely helpful.

WRT taxon constraints: feedback from @colinlog is that in marsupials indeed, the paternal X chromosome is inactivated throughout the body; however in mammals (including human) there is specific paternal X chromosome inactivation in the placenta, and random in the embryo proper. So I propose to only add the TC for only in Theria.

Could you please provide a reference that there is specific paternal X chromosome inactivation in human placenta. I saw numerous primary and review papers that said that this does not happen in humans. When I tried to find a paper that supported the idea that selective inactivation of the paternal X does occur in human placenta, I found this instead:

Phung TN, et al. X chromosome inactivation in the human placenta is patchy and distinct from adult tissues. HGG Adv. 2022 May 23;3(3):100121. Erratum in: HGG Adv. 2022 Sep 22;3(4):100142. PMID:35712697

Abstract:

In humans, one of the X chromosomes in genetic females is inactivated by a process called X chromosome inactivation (XCI). Variation in XCI across the placenta may contribute to observed sex differences and variability in pregnancy outcomes. However, XCI has predominantly been studied in human adult tissues. Here, we sequenced and analyzed DNA and RNA from two locations from 30 full-term pregnancies. Implementing an allele-specific approach to examine XCI, we report evidence that XCI in the human placenta is patchy, with large patches of either maternal or paternal X chromosomes inactivated. Further, using similar measurements, we show that this is in contrast to adult tissues, which generally exhibit mosaic X inactivation, where bulk samples exhibit both maternal and paternal X chromosome expression. Further, by comparing skewed samples in placenta and adult tissues, we identify genes that are uniquely inactivated or expressed in the placenta compared with adult tissues, highlighting the need for tissue-specific maps of XCI.

pgaudet commented 1 year ago

Hi @krchristie

Do you know which organisms have evidence for this process? You are right that the evidence is lacking, but @colinlog and I cannot find much evidence about other organisms either, so it would be conservative not to exclude humans for now.

krchristie commented 1 year ago

This Dupont and Gribnau review is one of my better sources of information. Because of the fact that this review indicated that studies involving human (and some other species) have been shown to only have random XCI, I thought it would be useful to add the "never in H. sapiens" taxon constraint to prevent errant annotations to imprinted XCI. We could add additional taxon constraints for the other species mentioned, but they aren't as important with respect to annotation.

Here's the relevant paragraph, along with the list of the references cited in the paragraph.

Dupont C, Gribnau J. Different flavors of X-chromosome inactivation in mammals. Curr Opin Cell Biol. 2013 Jun; 25(3):314-21. PMID:23578369.

XCI in other eutherian species The mouse has been the preferred model system to study eutherian XCI. In contrast to mice, however, recent studies involving human, non-human primates, and equine species indicate that XCI in these animals is restricted to the random form [67–69]. Thus far, besides mice, only rats and bovine species have been shown to display iXCI in extra-embryonic tissues [70–73].

  1. Moreira de Mello JC et al.: Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS ONE 2010, 5:e10947.

  2. Wang X et al.: Random X inactivation in the mule and horse placenta. Genome Res 2012, 22:1855-1863.

  3. Tachibana M et al.: X-chromosome inactivation in monkey embryos and pluripotent stem cells. Dev Biol 2012, 371:146-155.

  4. Xue F et al.: Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet 2002, 31:216-220.

  5. Dindot SV et al.: Conservation of genomic imprinting at the XIST, IGF2, and GTL2 loci in the bovine. Mamm Genome 2004, 15:966-974.

  6. Dindot SV et al.: Epigenetic and genomic imprinting analysis in nuclear transfer derived Bos gaurus/Bos taurus hybrid fetuses. Biol Reprod 2004, 71:470-478.

  7. Wake N, Takagi N, Sasaki M: Non-random inactivation of X chromosome in the rat yolk sac. Nature 1976, 262:580-581.

krchristie commented 1 year ago

I was looking for a really fantastic paper about use of mouse ES cells as a model for studying random XCI as it had a great diagram comparing zygotic genome activation timing and whether iXCI of the Xp occurred, but I can't find it again.

However, here is a great review about what DOES happen in human extraembryonic tissues and it also says that imprinted XCI does not happen in humans. I think that to add the taxon constraint "never in H. sapiens" to the term about "imprinted X inactivation of paternal X chromosome" would be consistent with the current view of X dosage compensation in humans. We could probabably add additional species to the "never in" list, but none as significant with respect to annotation as humans.

Sahakyan A, Plath K, Rougeulle C. Regulation of X-chromosome dosage compensation in human: mechanisms and model systems. Philos Trans R Soc Lond B Biol Sci. 2017 Nov 5; 372(1733):20160363. PMID:28947660

1. The X-chromosome state of the human pre-implantation embryo Petropoulos and colleagues studied the transcriptome of the largest number of human pre-implantation embryos reported to date, and performed sex-specific analysis of human development at days 3 – 7 post fertilization (E3–E7) at the single-cell level [2]. Their analysis revealed that immediately after zygotic gene activation (ZGA) at E4, female embryos had almost double expression of X-linked genes compared with males, consistent with females having two active X chromosomes (figure 1). However, with increasing developmental time from E4 to E7, this roughly 2 : 1 female : male ratio decreased, reaching nearly 1 : 1 in all cells of the embryo at E7 (figure 1), just in time for the commencement of implantation. Surprisingly, this drop in X-linked gene expression level was not due to the onset of X-chromosome-inactivation, because allelic expression analysis by single-cell RNA-sequencing revealed that both X chromosomes were active at all times [2]. Evidence for the presence of two active X chromosomes in female human pre-implantation embryos was extended further by RNA fluorescent in situ hybridization (RNA-FISH) [1,2,5,6]. Thus, Petropoulos et al. uncovered a novel mechanism of X-chromosome dosage compensation, at the mRNA level, in human pre-implantation development where female to male expression is equalized not by inactivating one of the two X chromosomes in the female, but rather by dampening the expression of both female X chromosomes (figure 1). This X-chromosome dampening (XCD), which has not been observed in mice, is reminiscent of the dosage compensation system occurring in a model organism further removed from the human on the evolutionary scale — the roundworm Caenorhabditis elegans. Both X chromosomes of XX hermaphrodite C. elegans undergo condensin-mediated three-dimensional structural remodelling, resulting in reduced transcriptional output to match X-linked gene dosage to that of the single X in XO males [7,8]. However, whether XCD in human and C. elegans are mechanistically similar remains an open question (see §2). In any case, together these findings indicate that X-chromosome dosage compensation in human is regulated by two different and sequential processes: first XCD and later XCI. Interestingly, moderate but significant expression asymmetry between the two X chromosomes was detected from E5, suggesting that X-linked gene silencing may initiate in a progressive manner at this developmental stage [5].

3. Differences between mouse and human XCI [snip] Early reports addressing the question of whether human early development follows what is observed in the mouse with respect to imprinted XCI have been mixed, but recent studies using more advanced techniques and larger sample sizes agree that human pre-implantation embryos lack imprinted XCI [1,2,22], and that, instead, human pre-implantation embryos reduce X-linked gene dosage by XCD on both X chromosomes [2]. Thus, in addition to XCD and XIST expression from an active X chromosome, the lack of imprinted XCI in human pre-implantation embryos is a key difference between mouse and human embryonic development. Interestingly, XIST expression and lack of imprinted XCI are also observed in rabbit pre-implantation development, despite the closer evolutionary distance between mouse and rabbit compared with rabbit and human [1].

krchristie commented 1 year ago

Hello Karen and Pascale, Browsing the publications that cite https://pubmed.ncbi.nlm.nih.gov/19802707/ it came to light that PMID: 22722828 reports another non-coding RNA than Xist, it is called Rsx and has the propeorties of Xist, including X-chromosome coating and exclusive expression by females. As it was found in marsuplials from Australia and from South America this is likely ancestral to all marsupials. This ncRNA was also detected in the Koala genome published in 2018 (PMID: 29967444). Hence, although Xist is not found in marsupials, the molecular mechanism and the biological processes of X-chromosome inactivation is likely conserved and incarnated by Rsx. @pgaudet @krchristie

Hi Colin, reading the Dupont & Gribnau review that I mentioned a couple comments ago, I see that they also comment that Rsx is thought to have a similar role in marsupials as Xist in eutherian mammals.

Dupont C, Gribnau J. Different flavors of X-chromosome inactivation in mammals. Curr Opin Cell Biol. 2013 Jun; 25(3):314-21. PMID:23578369.

[snip] To prevent overexpression of dosage-compensated X-linked genes in female animals, a second form of dosage compensation, resulting in the inactivation of one of the two X chromosomes in female cells, has evolved [6]. In eutheria, the non-coding RNA Xist [7–9] has been shown to be the central element for the initiation of X-chromosome inactivation (XCI), whereas in metatherians the recently discovered non-coding RNA Rsx has been proposed to have a similar role [10**].

However, the current definition of the term inactivation of paternal X chromosome by genomic imprinting (GO:0060818) is broad enough to accomodate either the marsupial (metatherian) or eutherian iXCI:

Def: Compensating for the two-fold variation in X-chromosome:autosome ratios between sexes by a global inactivation of all, or most of, the genes on the paternal X-chromosome in the XX sex by genomic imprinting.

I thought about trying to create more specific terms for eutherians, so that you could specify that both rXCI and iXCI in eutherians involve control of Xist. I hadn't caught that Rsx was considered to likely be the metatherian equivalent of eutherian Xist. However, considering the limited need to annotate marsupial genomes at present, it seemed unnecessarily complicated.

This Escamilla-Del-Arenal et al. review from 2011 suggests a hypothetical evolutionary timeline of XCI strategies in different mammals, specifically that the mouse form of iXCI re-evolves in a eutherian lineage leading to mice, which is consistent with the fact that it is quite different with the iXCI in metatherians. However, again related to the limited need to annotate marsupial genomes at present, it doesn't seem worth creating two specific forms of iXCI to be specific to metatherians or eutherians.

Escamilla-Del-Arenal M, da Rocha ST, Heard E. Evolutionary diversity and developmental regulation of X-chromosome inactivation. Hum Genet. 2011 Aug;130(2):307-27. doi: 10.1007/s00439-011-1029-2. Epub 2011 Jun 18. PMID: 21687993; PMCID: PMC3132430. 21687993-Escamilla-Del-Arenal_2011-XCI-F1

krchristie commented 1 year ago

GO:0060818 inactivation of paternal X chromosome by genomic imprinting

I noticed some minor editing errors on my part in the comment I suggested in the last sentence.

* [x]  add comment

Selective inactivation of the paternal X chromosome via imprinting is the only form of X chromosome inactivation in marsupials, though the mechanism there may be significantly different as marsupials the Xist or transcript is not present on metatherian X chromosomes.

change this to:

Selective inactivation of the paternal X chromosome via imprinting is the only form of X chromosome inactivation in marsupials, though the mechanism there may be significantly different in marsupials as the Xist transcript is not present on metatherian X chromosomes.

pgaudet commented 1 year ago

Thanks Karen. The ticket is linked in the term so we can always revisit later as more data is published, but for now this term is precise enough. I updated the comment.

Pascale

krchristie commented 1 year ago

Thanks Karen. The ticket is linked in the term so we can always revisit later as more data is published, but for now this term is precise enough. I updated the comment.

Pascale

Great. I thought so too.

Regarding the taxon constraints, did you add the "never in Homo sapiens". I think it would be a good idea both as the literature supports this and also to prevent inappropriate annotations.

krchristie commented 1 year ago

Regarding the taxon constraints, did you add the "never in Homo sapiens". I think it would be a good idea both as the literature supports this and also to prevent inappropriate annotations.

@pgaudet - I wanted to check if you added this taxon constraint. The literature is not controversial about this and it would be really helpful to prevent incorrect annotations for human genes by annotators who aren't super familiar with this area.

pgaudet commented 1 year ago

@krchristie done