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Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation

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Official URL:https://doi.org/10.1083/jcb.200502062
PubMed:View item in PubMed
Creators Name:Brero, A. and Easwaran, H.P. and Nowak, D. and Grunewald, I. and Cremer, T. and Leonhardt, H. and Cardoso, M.C.
Journal Title:Journal of Cell Biology
Journal Abbreviation:J Cell Biol
Page Range:733-743
Date:6 June 2005
Keywords:Cell Differentiation, Cultured Cells, Non-Histone Chromosomal Proteins, DNA Methylation, DNA-Binding Proteins, Genetic Epigenesis, Developmental Gene Expression Regulation, Heterochromatin, Histones, Methyl-CpG-Binding Protein 2, Skeletal Muscle, Skeletal Myoblasts, Tertiary Protein Structure, Recombinant Fusion Proteins, Repressor Proteins, Animals, Mice
Abstract: Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG-binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG-binding domain (MBD) only. Similar to MeCP2, another methyl CpG-binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation.
Publisher:Rockefeller University Press (U.S.A.)
Additional Information:Copyright (c) 2005 by Rockefeller University Press
Item Type:Article

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