B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.
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.
Johnson
Kristen
K
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Pflugh
David L
DL
Yu
Duonan
D
Hesslein
David G T
DG
Lin
Kuo-I
KI
Bothwell
Alfred L M
AL
Thomas-Tikhonenko
Andrei
A
Schatz
David G
DG
Calame
Kathryn
K
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology*; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006657:Histones / Q000737:chemistry*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008239:Lysine / Q000737:chemistry*; D008745:Methylation; D051379:Mice; D018448:Models, Immunological; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000276:immunology*
D004268:DNA-Binding Proteins; D006657:Histones; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors; D008239:Lysine