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

K Johnson, DL Pflugh, D Yu, DGT Hesslein, KI Lin… - Nature …, 2004 - nature.com
K Johnson, DL Pflugh, D Yu, DGT Hesslein, KI Lin, ALM Bothwell, A Thomas-Tikhonenko
Nature immunology, 2004nature.com
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 …
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.
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