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PMID: 15939760 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 169 ·No. 5 ·2005-06-06 ·Pages 733-43

Brero A, Easwaran HP, Nowak D, Grunewald I, Cremer T, Leonhardt H, Cardoso MC

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.

MeSH Terms
Animals Cell Differentiation/genetics Cells, Cultured Chromosomal Proteins, Non-Histone/genetics,metabolism DNA Methylation DNA-Binding Proteins/genetics,metabolism Epigenesis, Genetic/genetics Gene Expression Regulation, Developmental/genetics Heterochromatin/genetics,metabolism,ultrastructure Histones/genetics,metabolism Male Methyl-CpG-Binding Protein 2 Mice Mice, Inbred C57BL Mice, Transgenic Muscle, Skeletal/embryology,metabolism,ultrastructure Myoblasts, Skeletal/metabolism,ultrastructure Protein Structure, Tertiary/genetics Recombinant Fusion Proteins/genetics,metabolism Repressor Proteins/genetics,metabolism
Chemicals
Chromosomal Proteins, Non-Histone DNA-Binding Proteins Heterochromatin Histones Mbd2 protein, mouse Mecp2 protein, mouse Methyl-CpG-Binding Protein 2 Recombinant Fusion Proteins Repressor Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Brero Alessandro
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Easwaran Hariharan P
Nowak Danny
Grunewald Ingrid
Cremer Thomas
Leonhardt Heinrich
Cardoso M Cristina
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200502062
Published
2005-06-06
Pages
733-43
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171616
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200502062 PMC Full Text View journal details
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