Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment

Nucleic Acids Res. 2017 Nov 2;45(19):11070-11087. doi: 10.1093/nar/gkx722.


Genome organization in 3D nuclear-space is important for regulation of gene expression. However, the alterations of chromatin architecture that impinge on the B cell-fate choice of multi-potent progenitors are still unclear. By integrating in situ Hi-C analyses with epigenetic landscapes and genome-wide expression profiles, we tracked the changes in genome architecture as the cells transit from a progenitor to a committed state. We identified the genomic loci that undergo developmental switch between A and B compartments during B-cell fate determination. Furthermore, although, topologically associating domains (TADs) are stable, a significant number of TADs display structural alterations that are associated with changes in cis-regulatory interaction landscape. Finally, we demonstrate the potential roles for Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Collectively, our studies provide a general paradigm of the dynamic relationship between chromatin reorganization and lineage-specific gene expression pattern that dictates cell-fate determination.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Binding Sites / genetics
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Gene Expression Profiling / methods
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Chromatin
  • Ebf1 protein, mouse
  • Trans-Activators