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PTN000256565 not transcription #2063

Closed ValWood closed 6 years ago

ValWood commented 6 years ago

for pombe ned1

GO:1903508 | positive regulation of nucleic acid-templated transcription

from http://www.informatics.jax.org/marker/MGI:1891340 http://www.informatics.jax.org/marker/MGI:1891341

ned1 (lipin) a phosphatidate lipid phosphatase catalyzing the hydrolytic dephosphorylation of a phos- phatidate to a diacylglycerol. It controls cellular lipid homeostasis

nothing really to do with transcription, although the nuclear envelope deformations caused in mutants will certainly affect transcription, it isn't regulating transcription in a WT cell.

pgaudet commented 6 years ago

The yeast gene is also some sort of tx coregulator: https://www.ncbi.nlm.nih.gov/pubmed/15889145

Had you also looked at that reference ?

ValWood commented 6 years ago

I don't think its really a txn regulator.

This mutant is disturbing the nuclear membrane. During membrane stresses changes in inositol levels are detected, and this activates transcription of lipid biosynthesis genes. In a normal cell I don't think lipin is a transcriptional regulator. Thsi mutant is causing a problem that is sensed by some pathway and lipid bio genes are turned on. Certainly not enough info for GO for us.....because it is most likely just a phenotype.

(SGD did not make this annotation either)

pgaudet commented 6 years ago

They have 'transcription regulatory region DNA binding (IDA) ' https://www.yeastgenome.org/locus/S000004775

and looking at the paper cited (PMID:15889145) , including this part of the abstract

We show that Smp2 associates with the promoters of phospholipid biosynthetic enzymes in a Nem1-Spo7-dependent manner. Our data suggest that Smp2 is a critical factor in coordinating phospholipid biosynthesis at the nuclear/ER membrane with nuclear growth during the cell cycle.

I thought perhaps there was enough evidence from varied sources to make the annotations.

Pascale

ValWood commented 6 years ago

I had missed that annotation, but it isn't DNA binding

" Although Smp2 does not contain any sequence that might resemble a DNA-binding motif, it could be indirectly recruited to specific promoters by interaction with other factors. To test this possibility, we performed chromatin inmunoprecipitation of an Smp2-PtA fusion, followed by real-time PCR analysis. We found that a pool of Smp2 associates in fact with the INO1, INO2 and OPI3 promoters (Figure 8A, black bars). The amounts of Smp2 in these promoters oscillate between 3.4- and 4-fold over the background levels detected at an intergenic region in chromosome V. This interaction is specific since no significant amount of Smp2 could be detected at the promoters of unrelated genes such as MPP10 (Figure 8A)."

this is CHIp data. With some cherry picked genes. (chromatin association is expected since it is nuclear membrane...) the differences are between promoter association and hinge on one control gene.

pombe ortholog Ned1 has pleiotropic phenotypes: https://www.pombase.org/gene/SPAC1952.13 mainly as a consequence of nuclear envelope morphology problems.

I just wouldn't make a process GO annotation (or anything associating with specific promoters) from this paper, the data is just too weak. This might be why SGD curated the chromatin association assay but stopped short of a transcription process term. But I'm not sure why it's a"DNA binding" term rather than chromatin-associated.......also I don't think you can put genes as direct inputs for a DNA binding term , can you?

ValWood commented 6 years ago

I asked a couple of people just to be sure....

pgaudet commented 6 years ago

The experts contacted by @ValWood write

The budding yeast transcription circuit is not conserved outside budding yeasts (actually, a big chunk of inositol metabolism is different between the two clades). The mammalian data suggest a different mechanism and are not particularly direct either.

Our own (unpublished) data indicate that all transcriptional changes in pombe lipin deletion are due to the loss of its PA->DAG catalytic activity (the situation seems different in japonicus).

So what am trying to say, it is probably OK to say that such regulation has been picked up in other species but the extent to which it can be generalized is not clear. As a disclaimer, I might have missed something!

So I'll remove the propagation from the yeast clade.

Thanks, Pascale