B cell-specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5

Kristen Johnson, David L. Pflugh, Dounan Yu, David G.T. Hesslein, Kuo I. Lin, Alfred L.M. Bothwell, Andrei Thomas-Tikhonenko, David G. Schatz, Kathryn Calame

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Immunoglobulin heavy chain rearrangement (VH-to-DJH) occurs only in B cells, suggesting it is inhibited in other lineages. Here we found that in the mouse VH 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 VH-to-DJH 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 VH 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 VH-to-DJH recombination.

Original languageEnglish (US)
Pages (from-to)853-861
Number of pages9
JournalNature immunology
Volume5
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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