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

Cell Rep. 2020 Apr 7;31(1):107470. doi: 10.1016/j.celrep.2020.03.034.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / physiology
  • Chromosomes / genetics
  • Epigenesis, Genetic / genetics
  • Female
  • Genome / genetics
  • Heterochromatin / genetics
  • Histones / genetics
  • Histones / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plasma Cells / cytology
  • Plasma Cells / metabolism*
  • Plasma Cells / pathology
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Regulatory Sequences, Nucleic Acid / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism

Substances

  • Atf4 protein, mouse
  • Ebf1 protein, mouse
  • Heterochromatin
  • Histones
  • Trans-Activators
  • Transcription Factors
  • Activating Transcription Factor 4
  • Positive Regulatory Domain I-Binding Factor 1