Transgenic mouse study demonstrates increased CpG-island methylation in homozygous versus hemizygous states, suggesting trans-acting factor titration protects unmethylated DNA.
Methylation-free islands (MFIs), clusters of non-methylated CpG-dinucleotides in mammalian genomes, are associated with a majority of studied genes. By which precise mechanism they maintain their unmethylated status is unknown. The behaviour of transgenic MFIs may contribute to unveil this enigma. We have generated a high-copy number transgenic line with the MFI from the murine Thy-1.1 allele. A stable, minor fraction of this otherwise non-methylated DNA became completely methylated in all adult tissues tested. Furthermore, individuals homozygous for the transgene showed a significantly higher proportion of methylated copies compared to the hemizygous state. These findings support the hypothesis that a limited pool of trans-acting factors are involved in maintaining the hypomethylated state.
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Gundersen et al. (1991) studied this question.
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