DNA Methylation Dependent Chromatin Structures

Recent studies in the filamentous fungus Neurospora crassa and in Arabidop-sis thaliana revealed a close interaction between histone methylation and

DNA methylation. In Neurospora, dim-2-mediated DNA methylation has been shown to be dependent on the activity of the histone H3 methyltransferase dim-5 (Tamaru and Selker 2001). In Arabidopsis, CHROMOMETHYLASE3-mediated DNA methylation has been shown to be dependent on the activity of the histone H3 methyltransferase KRYPTONITE (Jackson et al. 2002). A similar interaction between DNA methylation and histone methylation can be also found in Drosophila. The Su(var)3-9 histone methyltransferase specifically methylates lysine 9 of histone H3 (H3K9) (Schotta et al. 2002). Because in Su(var)3-9 null mutant larvae H3K9 methylation was strongly reduced at the chromocenters, the protein seems to be specific for the methylation of histones in centromeric heterochromatin (Schotta et al. 2002). Null mutant flies for Su(var)3-9 are viable and fertile (Tschiersch et al. 1994), similar to knockout mice for the murine Drosophila Su(var)3-9 homologs Suv39hl and Suv39h2 (Peters et al. 2001). Immunofluorescence staining of Su(var)3-9-null mutant fly embryos revealed a dramatic reduction if not complete loss of DNA methylation (Kunert et al. 2003), demonstrating a conservation of the interaction between DNA methylation and histone methylation.

Moreover, histone methylation also plays an important role in the transmission of epigenetic information from DNA methylation to repressive chromatin structures. Ectopic expression of the mouse DNA methyltransferase DNMT3a in Drosophila leads to lethality, which is characterized by irregular chromosome condensation and dysregulation of histone modifications (Weissmann et al. 2003). This lethality could be partially rescued when the ectopic expression of DNMT3a was induced in a Su(var)3-9 mutant background (Weissmann et al. 2003). These data together with additional results from Arabidopsis suggest a mutual and complex relationship between DNA methylation and H3K9 methylation (Weissmann and Lyko 2003).

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