An alternative promoter in the mouse major histocompatibility complex class II I-Abeta gene: implications for the origin of CpG islands.

Nonmethylated CpG islands are generally located at the 5' ends of genes, but a CpG island in the mouse major histocompatibility complex class II I-Abeta gene is remote from the promoter and covers exon 2. We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells. The resulting transcript potentially encodes a severely truncated protein which would lack the signal peptide and external beta1 domains. The functional significance of the internal CpG island may be to facilitate gene conversion, thereby sustaining the high level of polymorphism seen at exon 2. Deletions of the I-Abeta CpG island promoter reduce transcription and frequently lead to methylation of the CpG island in a transgenic mouse assay. These and other results support the idea that all CpG islands arise at promoters that are active in early embryonic cells.