Matrix: MECP2 amino acid metabolic process/ cell cycle regulation

[ValWood]

This paper has a lot of annotation, and most should probably only be annotated as phenotypes are probably very indirect.. However, I don't see any experiments demonstrating either of these:

MECP2 | Methyl-CpG-binding protein 2 |   | positive regulation of cell population proliferation |   | CAFA | Homo sapiens | IMP |   | 5-methylcytosine g/t mismatch-specific dna glycosylase pthr15074 | protein |   | PMID:25527496 | 20170116

MECP2 | Methyl-CpG-binding protein 2 |   | positive regulation of G2/M transition of mitotic cell cycle |   | CAFA | Homo sapiens | IMP |   | 5-methylcytosine g/t mismatch-specific dna glycosylase pthr15074 | protein |   | PMID:25527496 | 20170116

(also ISO for rat need removing)

[ValWood]

This is a a bit specific based on these data.

Mecp2 | methyl CpG binding protein 2 |   | positive regulation of microtubule nucleation |   | RGD | Rattus norvegicus | ISO | RGD:1349232 | 5-methylcytosine g/t mismatch-specific dna glycosylase pthr15074 | gene |   | PMID:25527496RGD:1624291 | 20170318

For now "spindle organization" is probably overstretching the date , but I will leave that one for now. I will probably address this in more detail later with reasons why it isn't directly involved in this process.

[ValWood]

raised a dispute for. the CAFA annotation

[Antonialock]

I am a bit unsure what to change the annotation to.

from a more recent paper: Indeed, nowadays MeCP2 appears as a multifunctional protein that manifests different activities depending on its partners and post‐translational modifications...we have recently demonstrated that MeCP2 is functionally associated with centrosomes and, similarly to many centrosomal proteins, its deficiency causes aberrant spindle geometry, defects in cell proliferation, microtubule nucleation and prolonged mitosis. This novel function reconciled previous data regarding a role of MeCP2 in cell growth, cytoskeleton stability, and axonal transport https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278541/

it must have some real moonlighting function at the centrosome since it localizes there?

[ValWood]

Even if it has a centrosomal, a role in "cell cycle regulation" would be a stretch. That seems that it would be a phenotype, defect in spindle/ stuffs up cell cycle.

Cell population proliferation should be removed (that is only for use with for controlling proliferation of specific cell types ) - I don't think it should really be in GO

[Antonialock]

this might be a very stupid question, but I read that mecp2 is enriched at the centromere, could it just be anchored near the centrosome since it's peri-centromeric? At least in cerevisiae, the kinetochore goes to the SPB during most of the cell cycle and only comes off to replicate centromeric DNA in S phase (but are then recaptured) - I don't know much about this

[Antonialock]

"In vivo MeCP2 was shown to be enriched at pericentric heterochromatin [4]. Pericentric heterochromatin is localized in proximity to the centromere and enriched in AT-rich major satellite DNA repeats occupying about 10% of the mouse genome" -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226738/

[Antonialock]

in which case it could probably be linked back to its function at the chromatin level?

[ValWood]

Yeah I'm not convinced it is meaningful. All of the phenotypes could be explained by gene expression defects. But I know nothing about this particular either. I think I would want to see come real connection to a centrosomal function before I made any annotations around this observation.