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

doi:10.1038/ni1099

B cell-specific loss of histone 3 lysine 9 methylation in the V_H 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 journal › Article › peer-review

95 Scopus citations

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.

Original language	English (US)
Pages (from-to)	853-861
Number of pages	9
Journal	Nature immunology
Volume	5
Issue number	8
DOIs	https://doi.org/10.1038/ni1099
State	Published - Aug 2004
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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

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.",

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

year = "2004",

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T1 - B cell-specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5

AU - Johnson, Kristen

AU - Pflugh, David L.

AU - Yu, Dounan

AU - Hesslein, David G.T.

AU - Lin, Kuo I.

AU - Bothwell, Alfred L.M.

AU - Thomas-Tikhonenko, Andrei

AU - Schatz, David G.

AU - Calame, Kathryn

PY - 2004/8

Y1 - 2004/8

N2 - 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.

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

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