Poly(ADP-ribosyl)ation of Methyl CpG Binding Domain Protein 2 Regulates Chromatin Structure.

The Journal of Biological Chemistry
Annette BeckerM Cristina Cardoso

Abstract

The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphorylation and other posttranslational modifications of MeCP2 have been described recently to modulate its function. Here we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue. Consequently, we found that MeCP2 induced aggregation of pericentric heterochromatin and that its chromatin accumulation was enhanced in poly(ADP-ribose) polymerase (PARP) 1(-/-) compared with wild-type cells. We mapped the poly(ADP-ribosyl)ation domains and engineered MeCP2 mutation constructs to further analyze potential effects on DNA binding affinity and large-scale chromatin remodeling. Single or double deletion of the poly(ADP-ribosyl)ated regions and PARP inhibition increased the heterochromatin clustering ability of MeCP2. Increased chromatin clustering may reflect increased binding affinity. In agreement with this hypothesis, we found that PA...Continue Reading

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Citations

Jun 15, 2016·Briefings in Functional Genomics·Floriana Della RagioneMaurizio D'Esposito
Sep 30, 2016·Seminars in Cell & Developmental Biology·Melanija Posavec MarjanovićIvan Ahel
Dec 3, 2016·Seminars in Cell & Developmental Biology·Fabio CiccaronePaola Caiafa
Dec 8, 2016·Nucleic Acids Research·Anne K LudwigM Cristina Cardoso
Jan 10, 2017·Clinics and Research in Hepatology and Gastroenterology·Jing ZhaoKai Wang
Oct 11, 2017·Journal of Molecular Cell Biology·Min Hee ChoiReshma Taneja
Jun 3, 2020·Genes·Salvatore FiorinielloFloriana Della Ragione
Aug 21, 2019·Journal of Experimental & Clinical Cancer Research : CR·Erbao BianBing Zhao
Apr 9, 2020·Cells·Annika SchmidtM Cristina Cardoso
Dec 24, 2019·Journal of Molecular Biology·Haser H SutcuAlexander A Ishchenko
Jan 8, 2021·Frontiers in Cell and Developmental Biology·Tanaya Roychowdhury, Samit Chattopadhyay

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Methods Mentioned

BETA
PCR
Transfection
fluorescence recovery after photobleaching
pull down
immunoprecipitation
electrophoresis
flow cytometry
fluorescence imaging
immunoprecipitations
fluorescence recovery

Software Mentioned

ImageJ
Volocity
AMIRA
easyFRAP
Adobe Photoshop

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