Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs

The transition from the follicular B to the plasma cell stage is associated with large-scale changes in cell morphology. Here, we examine whether plasma cell development is also associated with changes in nuclear architecture. We find that the onset of plasma cell development is concomitant with a decline in remote genomic interactions; a gain in euchromatic character at loci encoding for factors that specify plasma cell fate, including Prdm1 and Atf4; and establishment of de novo inter-chromosomal hubs. We find that, in developing plasma cells and concurrent with transcriptional silencing, the Ebf1 locus repositions from an euchromatic to peri-centromeric heterochromatic environment. Finally, we find that inter-chromosomal hubs are enriched for the deposition of either H3K27Ac or H3K27me3. These data indicate that plasma cell fate is orchestrated by elaborate changes in genome topology and that epigenetic marks, linked with super-enhancers or transcriptionally repressed regions, are enriched at inter-chromosomal hubs. [Display omitted] •Plasma cell fate is orchestrated by elaborate changes in nuclear architecture•The Ebf1 locus relocates to the peri-centromeric heterochromatin in plasma cells•Plasma cell fate is associated with de novo inter-chromosomal hubs•Inter-chromosomal hubs are enriched for H3K27Ac or H3K27me3 Bortnick et al. demonstrate that plasma cell fate is associated with changes in chromatin folding, inter-chromosomal interactions, and nuclear localization involving plasma-cell-specific genes. Inter-chromosomal hubs in maturing B cells are enriched for the deposition of either H3K27Ac or H3K27me3. We propose that deposition of these marks facilitates inter-chromosomal interactions.