Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Research news

Targeted methylation

Jonathan Weitzman

Author Affiliations

Genome Biology 2000, 1:spotlight-20001221-01  doi:10.1186/gb-spotlight-20001221-01

The electronic version of this article is the complete one and can be found online at:


Published:21 December 2000

© 2000 BioMed Central Ltd

Research news

Methylation of DNA at CpG dinucleotides represses gene transcription. Methylation plays an important role in development, imprinting, X-chromosome inactivation and tissue-specific gene expression, but the mechanisms of methylation-induced repression are still unclear. In the December Molecular and Cellular Biology, Schubeler et al. show that localized histone deacetylation can explain methylation-induced repression (Mol Cell Biol 2000, 20:9103-9112). The authors used an elegant technique called recombinase-mediated cassette exchange (RMCE) to introduce in vitro-methylated DNA at defined chromosomal positions. They used the Cre recombinase to insert methylated or unmethylated forms of the human β-globin gene promoter driving a green fluorescent protein (GFP) reporter gene. Methylation repressed GFP expression, and was stable in cells over at least 12 weeks in culture. Methylation did not affect DNA replication or global chromatin remodeling. However, methylation caused a hypoacetylation of histones H3 and H4 within the transgene. These observations support a model in which methylated DNA represses local transcription by recruiting histone deacetylase activity.

References

  1. CpG methylation, chromatin structure and gene silencing-a three-way connection.

    PubMed Abstract | Publisher Full Text OpenURL

  2. [http://www.intl-mcb.asm.org] webcite

    Molecular and Cellular Biology

  3. Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange.

    PubMed Abstract | Publisher Full Text OpenURL