TUdatalib : MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation

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dc.contributor.author	Schmidt, Annika
dc.contributor.author	Frei, Jana
dc.contributor.author	Poetsch, Ansgar
dc.contributor.author	Chittka, Alexandra
dc.contributor.author	Aßmann, Chris
dc.contributor.author	Lehmkuhl, Anne
dc.contributor.author	Bauer, Uta-Maria
dc.contributor.author	Nuber, Ulrike
dc.contributor.author	Cardoso, Cristina
dc.contributor.author	Zhang, Hui
dc.date.accessioned	2022-05-09T16:43:11Z
dc.date.available	2022-05-09T16:43:11Z
dc.date.issued	2022
dc.identifier.uri	https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/3455
dc.identifier.uri	https://doi.org/10.48328/tudatalib-868
dc.description	Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked MECP2 gene. The epigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shown previously that MECP2 Rett syndrome missense mutations are impaired in chromatin binding and heterochromatin reorganization. Here, we performed a proteomics analysis of post-translational modifications of MeCP2 isolated from adult mouse brain. We show that MeCP2 carries various post-translational modifications, among them phosphorylation on S80 and S421, which lead to minor changes in either heterochromatin binding kinetics or clustering. We found that MeCP2 is (di)methylated on several arginines and that this modification alters heterochromatin organization. Interestingly, we identified the Rett syndrome mutation site R106 as a dimethylation site. In addition, co-expression of protein arginine methyltransferases 1 and 6 lead to a decrease of heterochromatin clustering. Altogether, we identified and validated novel modifications of MeCP2 in the brain and show that these can modulate its ability to bind as well as reorganize heterochromatin, which may play a role in the pathology of Rett syndrome.	de_DE
dc.language.iso	en	de_DE
dc.rights	Creative Commons Attribution-NonCommercial 4.0
dc.rights.uri	https://creativecommons.org/licenses/by-nc/4.0/
dc.subject	Arginine (di)methylation	de_DE
dc.subject	Heterochromatin organization	de_DE
dc.subject	MeCP2	de_DE
dc.subject	Protein arginine methyltransferases	de_DE
dc.subject	Rett syndrome	de_DE
dc.subject.classification	2.11-03 Zellbiologie	de_DE
dc.subject.ddc	570
dc.title	MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation	de_DE
dc.type	Software	de_DE
dc.type	Image	de_DE
dc.description.version	Public access	de_DE
tud.project	DFG \| CA198/10-1 \| Interaktion zwischen	de_DE
tud.project	DFG \| CA198/16-1 \| Rölle und Regulation	de_DE
tud.project	DFG \| NU119/3-1 \| Interaktion zwischen	de_DE
tud.unit	TUDa
tud.history.classification	Version=2020-2024;201-03 Zellbiologie