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 exclusively from the paternal allele. We found that U2af1-rs1 resides in a chromosomal domain that displays marked differences in chromatin conformation and DNA methylation between the parental chromosomes. Chromatin conformation was assayed in brain and liver, in fetuses, and in embryonic stem cells by sensitivity to nucleases in nuclei. In all these tissues, the unmethylated paternal chromosome is sensitive to DNase-I andMspI and has two DNase-I hypersensitive sites in the 5′-untranslated region. In brain and in differentiated stem cells, which display high levels of U2af1-rs1 expression, a paternal DNase-I hypersensitive site is also readily apparent in the promoter region. On the maternal chromosome, in contrast, the entireU2af1-rs1 gene and its promoter are highly resistant to DNase-I and MspI in all tissues analyzed and are fully methylated. No differential MNase sensitivity was detected in this imprinted domain. The parental chromosome-specific DNA methylation and chromatin conformation were also present in parthenogenetic and androgenetic cells and in tissues from animals maternally or paternally disomic for chromosome 11. This demonstrates that these parental chromosome-specific epigenotypes are independently established and maintained and provides no evidence for interallelictrans-sensing and counting mechanisms inU2af1-rs1.