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| Item Type: | Article |
|---|---|
| Title: | Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation |
| Creators Name: | Brero, A., Easwaran, H.P., Nowak, D., Grunewald, I., Cremer, T., Leonhardt, H. and Cardoso, M.C. |
| 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. |
| 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 |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 169 |
| Number: | 5 |
| Page Range: | 733-743 |
| Date: | 6 June 2005 |
| Additional Information: | Copyright (c) 2005 by Rockefeller University Press |
| Official Publication: | https://doi.org/10.1083/jcb.200502062 |
| PubMed: | View item in PubMed |
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