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

Alessandro Brero, Hariharan P. Easwaran, Danny Nowak, Ingrid Grunewald, Thomas Cremer, Heinrich Leonhardt, M. Cristina Cardoso

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalJournal of Cell Biology
Issue number5
StatePublished - Jun 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation'. Together they form a unique fingerprint.

Cite this