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Gene expression

The amazing demethylase

Nature volume 397, pages 568–569 (1999)Cite this article

DNA methylation is important for mediating repression of gene expression during mammalian development. But although much is known about how methyl groups are added to DNA, little has been done to work out how they are taken off. In an exciting article on page 579 of this issue, Bhattacharya et al.1 report that they have cloned a hitherto unknown gene which codes for a protein with a remarkable property — it can catalyse demethylation by directly removing methyl groups from 5-methyl-cytosine residues in DNA.

During normal development, cytosines in the dinucleotide CpG undergo a sequence of methylation and demethylation events, which are programmed to set up a defined methylation pattern (in both somatic and germline cells). This, in turn, plays a role in regulating gene expression. Soon after fertilization, a massive wave of demethylation erases almost all methyl groups in the genome, but the basic pattern is re-established at about the time the embryo is implanted in the uterus2, 3. This remethylation is mostly nonspecific, but CpG islands (mainly found in the promoter regions of ‘housekeeping’ genes) are protected from this process — probably by specific demethylation4. Later in development, many tissue-specific genes are demethylated in the cell type in which they are expressed. In all of these cases, the conversion of 5-methyl-cytosine to cytosine takes place through an active process which does not require DNA replication4,5,6.

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Figure 1: Mechanism for the enzymatic demethylation of 5-methyl-cytosine.

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Authors and Affiliations

  1. the Department of Cellular Biochemistry, Hebrew University Medical School, 91120, Jerusalem, Israel

    Howard Cedar

  2. the Department of Chemistry and Chemical Biology, and the Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, 02138, Massachusetts, USA

    Gregory L. Verdine

Authors
  1. Howard Cedar
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  2. Gregory L. Verdine
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Cedar, H., Verdine, G. The amazing demethylase. Nature 397, 568–569 (1999). https://doi.org/10.1038/17492

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