A PATERNAL-SPECIFIC METHYLATION IMPRINT MARKS THE ALLELES OF THE MOUSE H19 GENE

Imprinting, the differential expression of the two alleles of a gene b ased on their parental origin, requires that the alleles be distinguis hed or marked. A candidate for the differentiating mark is DNA methyla tion. The maternally expressed H19 gene is hypermethylated on the inac tive paternal allele in somatic tissues and sperm, but to serve as the mark that designates the imprint, differential methylation must also be present in the gametes and the pre-implantation embryo. We now show that the pattern of differential methylation in the 5' portion of H19 is established in the gametes and a subset is maintained in the pre-i mplanation embryo. That subset is sufficient to confer monoallelic exp ression to the gene in blastocysts. We propose that paternal-specific methylation of the far 5' region is the mark that distinguishes the tw o alleles of H19.