Heterochromatin Reorganization during Early Mouse Development Requires a Single-Stranded Noncoding Transcript

• Transcription, but not replication, is essential for clustering of PHC at the two-cell stage
• Major satellite transcripts are required for reorganization of maternal and paternal PHC
• Only the reverse strand of major satellite RNA is necessary for PHC clustering

SummaryThe equalization of pericentric heterochromatin from distinct parental origins following fertilization is essential for genome function and development. The recent implication of noncoding transcripts in this process raises questions regarding the connection between RNA and the nuclear organization of distinct chromatin environments. Our study addresses the interrelationship between replication and transcription of the two parental pericentric heterochromatin (PHC) domains and their reorganization during early embryonic development. We demonstrate that the replication of PHC is dispensable for its clustering at the late two-cell stage. In contrast, using parthenogenetic embryos, we show that pericentric transcripts are essential for this reorganization independent of the chromatin marks associated with the PHC domains. Finally, our discovery that only reverse pericentric transcripts are required for both the nuclear reorganization of PHC and development beyond the two-cell stage challenges current views on heterochromatin organization.

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