PARENTAL CHROMOSOME-SPECIFIC CHROMATIN CONFORMATION IN THE IMPRINTED U2AF1-RS1 GENE IN THE MOUSE

The imprinted U2af1-rs1 gene on mouse chromosome 11 is expressed exclu sively from the paternal allele. We found that U2af1-rs1 resides in a chromosomal domain that displays marked differences in chromatin confo rmation and DNA methylation between the parental chromosomes. Chromati n conformation was assayed in brain and liver, in fetuses, and in embr yonic stem cells by sensitivity to nucleases in nuclei. In all these t issues, the unmethylated paternal chromosome is sensitive to DNase-I a nd MspI and has two DNase-I hypersensitive sites in the 5'-untranslate d region. In brain and in differentiated stem cells, which display hig h levels of U2af1-rs1 expression, a paternal DNase-I hypersensitive si te is also readily apparent in the promoter region. On the maternal ch romosome, in contrast, the entire U2af1-rs1 gene and its promoter are highly resistant to DNase-I and MspI in all tissues analyzed and are f ully methylated. No differential MNase sensitivity was detected in thi s imprinted domain. The parental chromosome-specific DNA methylation a nd chromatin conformation were also present in parthenogenetic and and rogenetic cells and in tissues from animals maternally or paternally d isomic for chromosome 11. This demonstrates that these parental chromo some-specific epigenotypes are independently established and maintaine d and provides no evidence for interallelic trans-sensing and counting mechanisms in U2af1-rs1.