PXD033696

PXD033696 is an original dataset announced via ProteomeXchange.

Title	MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation
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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:23:31.818.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	M. Cristina Cardoso
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue; phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-05 01:11:06	ID requested
1	2022-10-14 21:53:01	announced
⏵ 2	2023-11-14 07:23:32	announced	2023-11-14: Updated project metadata.

Schmidt A, Frei J, Poetsch A, Chittka A, Zhang H, A, ß, mann C, Lehmkuhl A, Bauer UM, Nuber UA, Cardoso MC, MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation. Front Cell Dev Biol, 10():941493(2022) [pubmed]

submitter keyword: LC-MS/MS, brain, mouse

M. Cristina Cardoso
contact affiliation	Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
contact email	cardoso@bio.tu-darmstadt.de
lab head
M. Cristina Cardoso
contact affiliation	Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
contact email	cardoso-lab@bio.tu-darmstadt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033696
     1. Label: PRIDE project
     2. Name: MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation