New Twists on the Epigenetics of CpG Islands

  1. Rolf Ohlsson1 and
  2. Chandrasekhar Kanduri
  1. Department of Development and Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden

This extract was created in the absence of an abstract.

CpG islands are >200-bp stretches of DNA that have a significantly higher concentration of CpG dinucleotides than the bulk of the genome. Whereas 70%–80% of all CpG dinucleotides in the human genome are methylated, CpG islands by and large remain unmethylated (Cross and Bird 1995), with the exception of those associated with imprinted and X-linked genes (Razin and Cedar 1994). In this issue ofGenome Research, Strichman-Almashanu et al. (2002) present the first successful systematic approach to generating libraries of differentially methylated and unique CpG islands and show its use in uncovering novel imprinted genes.

Methylated CpG Islands and Genomic Imprinting

Figure 1 outlines the strategy used to select fragments that were subsequently cloned and sequenced. Whereas the majority of the clones isolated in this manner corresponded to CpG islands, most of the several hundred clones represented CpG island repeats, such as the nontranscribed intergenic spacer of ribosomal DNA and a transposon repeat, termed SVA. The library was further processed, therefore, to generate clones that were all determined to be CpG islands. Southern analysis of the library revealed that the clones fell into two categories: those that are densely methylated on both alleles both in soma and in sperm (termed SMRs) and those differentially methylated (termed gDMRs), as determined by analyzing DNA of uniparental tissues presumably displaying epigenetic states of maternal or paternal origin.

Figure 1.

Generation of differentially methylated CpG island library. Unfilled lollipops represent unmethylated CpGs and filled lollipops represent methylated CpGs. See text for details. (Revised from Fig. 1 ofStrichman-Almashanu et al. 2002, with permission.)

One of the differentially methylated sequences of the CpG island library of Strichman-Almashanu et al. (2002) mapped to a previously known imprinted gene, HYMA1. Encouraged by this …

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