Fig. 3.

Establishment of DNA methylation at the CDKN1C/KCNQ1OT1 imprinted locus. (A) The transcription of Kcnq1 in mouse oocytes is postulated to establish maternal-allele-specific methylation on KvDMR1, which silences maternal Kcnq1ot1 expression in the progeny. The allele-specific regulation of this cluster is conserved in humans. (B) Truncating the maternal Kcnq1 transcript in mice [Ap/YJ11 (Singh et al., 2017)] resulted in hypomethylation on the maternal KvDMR1. In humans, maternally inherited mutations, which disrupt KCNQ1 transcription, are hypothesized to disrupt the establishment of methylation on maternal IC2, which can lead to LoM on IC2 in the progeny (Niemitz et al., 2004; Beygo et al., 2019; Valente et al., 2019). See text for details.