Global changes in the nuclear positioning of genes and intra- and interdomain genomic interactions that orchestrate B cell fate

Nat Immunol. 2012 Dec;13(12):1196-204. doi: 10.1038/ni.2432. Epub 2012 Oct 14.


The genome is folded into domains located in compartments that are either transcriptionally inert or transcriptionally permissive. Here we used genome-wide strategies to characterize domains during B cell development. Structured interaction matrix analysis showed that occupancy by the architectural protein CTCF was associated mainly with intradomain interactions, whereas sites bound by the histone acetyltransferase p300 or the transcription factors E2A or PU.1 were associated with intra- and interdomain interactions that are developmentally regulated. We identified a spectrum of genes that switched nuclear location during early B cell development. In progenitor cells, the transcriptionally inactive locus encoding early B cell factor (Ebf1) was sequestered at the nuclear lamina, which thereby preserved their multipotency. After development into the pro-B cell stage, Ebf1 and other genes switched compartments to establish new intra- and interdomain interactions associated with a B lineage-specific transcription signature.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • CCCTC-Binding Factor
  • Cell Lineage*
  • Cell Nucleus / genetics*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Lymphopoiesis*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Lamina / metabolism
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / physiology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • p300-CBP Transcription Factors / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • CCCTC-Binding Factor
  • Ctcf protein, mouse
  • DNA-Binding Proteins
  • Ebf1 protein, mouse
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Tcf3 protein, mouse
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor

Associated data

  • GEO/GSE40173