Parallel tracking dosage compensation in the early mouse embryo

We develop So-Smart-seq to interrogate a comprehensive transcriptome inclusive of coding, noncoding, and repetitive element transcription. We reveal that, surprisingly, de novo silencing pertains only to a subset of paternal X (Xp) genes. In contrast, a set of evolutionarily older genes and LINEs demonstrate constitutive Xp silencing, adopt epigenetically distinct signatures, and do not require Xist to initiate silencing. On maternal X (Xm), however, these elements are hyperactivated. Thus, a significant subset of Xp elements appears to be inherited in a “pre-inactive” state. We also find that Xm-hyperactivation is timed to Xp silencing on an individual gene basis, giving rise to heterogeneity in the parallel track of dosage compensation as well. These conclusions have significant implications for the mechanism and evolution of imprinting in early mammals.