Allele-specific chromosome conformations induced by a transgene- and locus-dependent imprinting

A reporter transgene displayed parental imprinting in mouse embryos when positioned into the Itga6 gene. The strong lacZ pattern of expression scored in embryos inheriting the transgene from a male was not present when transmitted from a female. The transgene exhibited maternal allele-specific DNA hyper-methylation acquired in the germ-line and histone modifications corresponded to profiles described at known imprinted loci. Chromosome conformation analyzes revealed distinct, parent-of-origin interaction domains, with a more compact structure characterizing the maternally inherited repressed allele. The analysis of such transgene insertions with a selective potential to induce imprinting may help understanding the mechanisms identifying particular loci as targets for allele-specific repression. Data were quantile normalized within 4C/input replicate groups and scaled to medial feature intensity of 100 using TAS software (Affymetrix), generating signal.bar files. For each genomic position, a data set was generated consisting of all (PM-MM) pairs mapping within a sliding window of 250 bp. For Inv(rel5-Itga6) tissues, two independent 4C experiments were performed and merged in the .bar file.