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© 1993 Oxford University Press

OTHER

A methylated CpG island 3' in the apolipoprotein-E gene does not repress its transcription

Frank Larsen, Jorun Solheim and Hans Prydz*

Biotechnology Centre of Oslo, University of Oslo Postbox 1125, Blindern, N0317 Oslo, Norway

* To whom correspondence should be addressed

Received December 24, 1992; Revised April 7, 1993; Accepted April 7, 1993

CpG islands are always associated with the 5' end of housekeeping genes, covering their promoters and transcription start sites. CpG islands associated with genes of limited expression are less uniformly localized; the genes for apolipoprotein-E and -AI contain CpG islands corresponding to their last exons. As expected, the CpG island in the apo-AI gene is unmethylated in DNA from all tissues analyzed, expressing as well as non-expressing apolipoprotein-AI. In contrast, the apo-E CpG island is methylated in DNA from all tissues analyzed except sperm. The apo-E gene is transcribed in many tissues and is not repressed by this methylation. This establishes a functional difference between 5' and 3' CpG islands, because methylation of the former invariably leads to transcriptional repression. A similar methylation pattern was seen in the rat apo-E gene, which implies that this pattern probably was established before the divergence of rodents and primates. The numerous human apo-E alleles resulting from CpG to TpG/CpA mutations in the CpG island (i.e. deamination of methylated cytosine to thymine) suggest that this island is less protected from methylation in germ line than typical CpG islands.


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