Transcription outcome of promoters enriched in histone variant H3.3 defined by positioning of H3.3 and local chromatin marks.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Replication-independent histone variant H3.3 is incorporated into distinct genomic regions including promoters. However topology of promoter-associated H3.3 in relation to chromatin modifications and transcriptional outcome is not known, providing no insight on any distinction between H3.3-containing active and inactive promoters. Here, we report algorithms providing information on gene expression status as a function of density and position of multiple chromatin marks on promoters. We identify a relationship between promoter enrichment in epitope-tagged H3.3 or its canonical isoform H3.2 and corresponding transcriptional outcomes, as a function of sub-promoter positioning of DNA methylation and H3K4me3, H3K9me3 and H3K27me3. We identify a low-frequency configuration of H3.3 and H3K9me3 co-occupancy associated with transcriptional activity, while H3.3 and H3K27me3 promoters are invariably inactive. We unveil H3.3 and DNA methylated promoters whose transcription outcome depends on H3.3 sub-promoter positioning. Our results indicate how spatially restricted positioning of H3.3 may add another layer of transcription regulation.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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