The mechanisms underlying the role of A/B in the tissue-specific silencing of paternal Gsα expression are not well understood. Considering that the A/B transcription takes place more broadly than does paternal Gsα silencing, a mechanism that involves simple competition between the promoters of these two transcripts is unlikely. On the other hand, a plausible hypothesis involves a mechanism whereby the paternal A/B DMR binds either a repressor that directly silences the Gsα promoter or an insulator that prevents the effects of an upstream enhancer on the Gsα promoter. A mechanism similar to the latter has been demonstrated for the Igf2-H19 locus, in which methylation-sensitive binding of CTCF hinders Igf2 enhancer activity [91, 92]. To address these possibilities, it may be necessary to generate and study additional mouse models in which A/B transcript is disrupted without the deletion of its promoter region.
