B cell differentiation is associated with reprogramming the CCCTC binding factor-dependent chromatin architecture of the murine MHC class II locus

J Immunol. 2014 Apr 15;192(8):3925-35. doi: 10.4049/jimmunol.1303205. Epub 2014 Mar 14.


The transcriptional insulator CCCTC binding factor (CTCF) was shown previously to be critical for human MHC class II (MHC-II) gene expression. Whether the mechanisms used by CTCF in humans were similar to that of the mouse and whether the three-dimensional chromatin architecture created was specific to B cells were not defined. Genome-wide CTCF occupancy was defined for murine B cells and LPS-derived plasmablasts by chromatin immunoprecipitation sequencing. Fifteen CTCF sites within the murine MHC-II locus were associated with high CTCF binding in B cells. Only one-third of these sites displayed significant CTCF occupancy in plasmablasts. CTCF was required for maximal MHC-II gene expression in mouse B cells. In B cells, a subset of the CTCF regions interacted with each other, creating a three-dimensional architecture for the locus. Additional interactions occurred between MHC-II promoters and the CTCF sites. In contrast, a novel configuration occurred in plasma cells, which do not express MHC-II genes. Ectopic CIITA expression in plasma cells to induce MHC-II expression resulted in high levels of MHC-II proteins, but did not alter the plasma cell architecture completely. These data suggest that reorganizing the three-dimensional chromatin architecture is an epigenetic mechanism that accompanies the silencing of MHC-II genes as part of the cell fate commitment of plasma cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism*
  • Binding Sites
  • CCCTC-Binding Factor
  • Cell Differentiation*
  • Cell Line
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation
  • Genetic Loci*
  • H-2 Antigens / genetics*
  • H-2 Antigens / metabolism
  • Mice
  • Nucleotide Motifs
  • Plasma Cells / cytology
  • Plasma Cells / metabolism
  • Position-Specific Scoring Matrices
  • Promoter Regions, Genetic
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*


  • CCCTC-Binding Factor
  • CTCF protein, human
  • Chromatin
  • Ctcf protein, mouse
  • H-2 Antigens
  • Repressor Proteins

Associated data

  • GEO/GSE44637