A novel epigenetic control operating on Vme1(+) locus leads to variegated monoallelic expression

Vme1, located near an imprinted region containing Peg1/Mest, Copg2, and Mir 1/Lb9 on mouse chromosome 6, was identified and characterized to be under n ovel epigenetic regulations mediating nonimprinted monoallelic expression. The gene was transcribed independently from at least four promoters and alt ernatively spliced, Variable expression of the gene was found among individ uals and was not affected by genetic backgrounds, in contrast to a relative ly consistent expression of unlinked Peg3 under different genetic backgroun ds, Monoallelic expression of the gene was confirmed in several tissues of hybrid F1s between a domesticus and a molossinus subspecies. The nature of monoallelic expression was different from those of its neighboring genes wi th respect to the allelic preference for the expression, The observed varia ble expression and monoallelic expression propose a mechanism that operates to variegate the Vme1 transcription acting asynchronously on parental alle les, In addition, we observed that some biallelically expressed tissues exh ibited allele-specific splicing such that expression from one parental alle le yields elongated splice variants, whereas the other allele is spliced in to a short version, This unusual finding suggests that an epigenotype of th e promoter can determine the splicing fate of the transcript. (C) 2000 Acad emic Press.