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MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation

Schmidt, Annika ; Frei, Jana ; Poetsch, Ansgar ; Chittka, Alexandra ; Zhang, Hui ; Aßmann, Chris ; Lehmkuhl, Anne ; Bauer, Uta-Maria ; Nuber, Ulrike A. ; Cardoso, M. Cristina (2022)
MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation.
In: Frontiers in cell and developmental biology, 10
doi: 10.3389/fcell.2022.941493
Article, Bibliographie

Abstract

Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked gene. The epigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shown previously that 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 (PRMT)1 and PRMT6 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.

Item Type: Article
Erschienen: 2022
Creators: Schmidt, Annika ; Frei, Jana ; Poetsch, Ansgar ; Chittka, Alexandra ; Zhang, Hui ; Aßmann, Chris ; Lehmkuhl, Anne ; Bauer, Uta-Maria ; Nuber, Ulrike A. ; Cardoso, M. Cristina
Type of entry: Bibliographie
Title: MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation
Language: English
Date: September 2022
Journal or Publication Title: Frontiers in cell and developmental biology
Volume of the journal: 10
DOI: 10.3389/fcell.2022.941493
Abstract:

Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked gene. The epigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shown previously that 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 (PRMT)1 and PRMT6 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.

Identification Number: pmid:36172281
Additional Information:

Artikel-ID: 941493

Divisions: 10 Department of Biology
10 Department of Biology > Stem Cell and Developmental Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 10 Oct 2022 10:09
Last Modified: 11 Oct 2022 05:54
PPN: 500247579
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