Biallelic non-productive enhancer-promoter interaction precedes imprinted expression of KcnK9 during mouse neural commitment [RNA-seq]
How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood at most imprinted loci. To gain insight into the regulation of the Peg13-KcnK9 domain, an imprinted domain with important brain functions, during neural commitment, we performed a detailed integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression in the embryonic brain. We have evidence that despite an allelic higher order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts can occur on both alleles, although they are only productive on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side, and suggests a more nuanced role for allelic CTCF binding at the ICR of this locus. Overall design: RNA-seq  generated on ES and NP cells for B6 x JF1 and JF1 x B6 genetic backgrounds.