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First published online April 5, 2005

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Different sounds of gene silence

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 system and other aspects of heterochromatin structure and suggest that DNA methylation acts as a toggle between facultative and constitutive heterochromatin.

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DNA CpG hypomethylation induces heterochromatin reorganization involving the histone variant macroH2A

Yinghong Ma, Stephanie B. Jacobs, Laurie Jackson-Grusby, Mary-Ann Mastrangelo, José A. Torres-Betancourt, Rudolf Jaenisch, and Theodore P. Rasmussen
JCS 2005 118: 1607-1616. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content