Transcription Across the H19/Igf2 Imprinting Control Region Initiates Paternally Methylated Imprinting in Mouse Prospermatogonia (ChIP-Seq)
The insulator model explains the workings of the H19 and Igf2 domain in the soma, where insulation of the Igf2 promoter from its enhancers occurs by CTCF in the maternally inherited unmethylated chromosome but not the paternally inherited methylated allele. The molecular mechanism that targets paternal methylation imprint establishment to the imprinting control region (ICR) in the male germline is unknown. We tested the function of a prospermatogonia-specific broad low-level transcription in this process using mouse genetics. Paternal imprint establishment was abnormal when transcription was stopped at the entry point to the ICR. The germline epimutation persisted into the paternal allele of the soma, resulting in reduced Igf2 in fetal organs, and reduced fetal growth, consistent with the insulator model and IGF2's role as fetal growth factor. In summary, broad low-level transcription through the ICR initiates paternal imprint establishment at the H19/Igf2 ICR in the male germ line, with implications for Silver-Russell syndrome. The superseries contains RNAseq and ChIPseq data from 15.5 dpc fetal male germ cells that carry the RNA terminator cassette and also from control wild type mice. Overall design: Four different antiboies and input ChIP for wild type and H19 ter/H19 ter homozygous genotypes.