B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5

Nat Immunol. 2004 Aug;5(8):853-61. doi: 10.1038/ni1099. Epub 2004 Jul 18.

Abstract

Immunoglobulin heavy chain rearrangement (V(H)-to-DJ(H)) occurs only in B cells, suggesting it is inhibited in other lineages. Here we found that in the mouse V(H) locus, methylation of lysine 9 on histone H3 (H3-K9), a mark of inactive chromatin, was present in non-B lineage cells but was absent in B cells. As others have shown that H3-K9 methylation can inhibit V(D)J recombination on engineered substrates, our data support the idea that H3-K9 methylation inhibits endogenous V(H)-to-DJ(H) recombination. We also show that Pax5, a transcription factor required for B cell commitment, is necessary and sufficient for the removal of H3-K9 methylation in the V(H) locus and provide evidence that one function of Pax5 is to remove this inhibitory modification by a mechanism of histone exchange, thus allowing B cell-specific V(H)-to-DJ(H) recombination.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Base Sequence
  • Cell Lineage / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / immunology*
  • Flow Cytometry
  • Gene Rearrangement, B-Lymphocyte
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Histones / chemistry*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics*
  • Lysine / chemistry*
  • Methylation
  • Mice
  • Models, Immunological
  • Molecular Sequence Data
  • PAX5 Transcription Factor
  • Precipitin Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / immunology*

Substances

  • DNA-Binding Proteins
  • Histones
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Transcription Factors
  • Lysine