INACTIVE ALLELE-SPECIFIC METHYLATION AND CHROMATIN STRUCTURE OF THE IMPRINTED GENE U2AF1-RS1 ON MOUSE CHROMOSOME-11

The imprinted U2af1-rs1 gene that maps to mouse chromosome 11 is predo minately expressed from the paternal allele. We examined the methylati on of genomic sequences in and around the U2af1-rs1 locus to establish the extent of sequence modifications that accompanied the silencing o f the maternal allele. The analysis of HapII or HhaI sites showed that the silent maternal allele was hypermethylated in a block of CpG sequ ences that covered more than 10 kb. By comparison, the expressed pater nal allele was unmethylated from a CpG island upstream of the transcri bed region through 2 kb. An analysis of DNaseI hypersensitivity of a p utative promoter of U2af1-rs1 showed an open chromatin conformation on ly on the unmethylated, expressed paternal allele. These results sugge st that allele-specific hypermethylation covering the gene and its ups tream CpG island plays a role in maternal allele repression of U2af1-r s1, which is reflected in altered chromatin conformation of DNaseI hyp ersensitive sites. (C) 1996 Academic Press Inc.