Epigenetic complexity during the zebrafish mid-blastula transition.

The zebrafish developmental transcription program is determined by temporal post-translational histone modifications established in a step-wise and combinatorial manner on specific promoters around the time of zygotic genome activation (ZGA). Here, we characterize this increasing epigenetic complexity before, during and after ZGA. H3K4me3/H3K27me3 co-enrichment prevails over H3K4me3/H3K9me3 at the time of ZGA. Whereas most H3K4me3-marked promoters are devoid of transcriptionally repressive H3K9me3 or H3K27me3, the latter marks rarely occur in absence of H3K4me3. On co-enriched genomic regions, H3K4me3 and H3K27me3 can overlap regardless of H3K9me3 enrichment, but H3K4me3 and H3K9me3 are mutually exclusive. H3K4me3 and H3K9me3 may however overlap only when H3K27me3 also marks the overlapping domain, suggesting that H3K27me3 may modulate chromatin states. On metagenes, H3K27me3 enrichment correlates with local alteration in H3K4me3 density, and co-enrichment in H3K9me3 is linked to alterations in both H3K27me3 and H3K4me3 profiles. This suggests physical proximity of these marks and supports a view of existence of bi- or tri-valent chromatin domains. Thus enrichment in trimethylated H3K9 or H3K27 is associated with local remodeling of chromatin manifested by changes in H3K4me3 density. We propose that metagenes can provide information on the multivalency of chromatin sates.