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A proven role for methylation

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Cytosine methylation has been proposed to modulate tissue-specific expression, but compelling evidence has been hard to find. In an Advanced Online Publication in Nature Genetics, Futscher et al. describe a clear example of cell type-specific gene regulation by DNA methylation (Nature Genetics 20 May 2002, DOI:10.1038/ng886). They studied the maspin gene SERPINB5, expression of which is restricted to epithelial cells, and show, by bisulfite sequencing, that CpG sites in the SERPINB5 promoter were unmethylated in maspin-positive cells. Chromatin immunoprecipitation experiments using antibodies specific for acetylated histones H3 and H4 revealed depleted acetylation in methylated SERPINB5-negative cells. Demethylation of the promoter by DNA methyltransferase inhibitors reactivated SERPINB5expression. These results indicate a clear relationship between cytosine methylation, histone acetylation and tissue-specific regulation.

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    Cytosine methylation and mammalian development.

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    Nature Genetics, [http://www.nature.com/ng/]

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    Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.

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Weitzman, J.B. A proven role for methylation. Genome Biol 3, spotlight-20020522-02 (2002) doi:10.1186/gb-spotlight-20020522-02

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Keywords

  • Bisulfite
  • Histone Acetylation
  • Chromatin Immunoprecipitation
  • Cytosine Methylation
  • Bisulfite Sequencing