Transcriptionally silent DNA in mammalian genomes falls into two broad classes. Constitutive heterochromatin (for example, pericentric heterochromatin) is characterised by heavy DNA methylation at CpG dinucleotides. Facultative heterochromatin (for example, the inactive X chromosome) contains less methylation and is enriched in the variant histone macroH2A. Theodore Rasmussen and colleagues now show that the loss of DNA methylation remodels pericentric heterochromatin, causing it to adopt a state reminiscent of facultative heterochromatin (see p. 1607). The authors investigate chromatin organization in embryonic stem (ES) cells and transformed fibroblasts lacking Dnmt1, which encodes the cytosine methyltransferase that maintains CpG methylation patterns. In both cell types, immunostaining for macroH2A colocalizes with staining for heterochromatin protein 1 (HP1), which marks pericentric heterochromatin. Reintroduction of a Dnmt1 transgene into Dnmt1–/– ES cells restores macroH2A to its normal localization in facultative heterochromatin. These results indicate that there is crosstalk between the DNA CpG methylation...

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