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PMID: 12514097 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments.

Genes & development ·Vol. 17 ·No. 1 ·2003-01-01 ·Pages 37-42

Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG

Abstract

Pax5-deficient progenitor B (pro-B) cells are thought to be severely defective for recombination of all immunoglobulin heavy chain (IgH) V gene segments, but the mechanism by which Pax5 regulates this process has not been defined. To address this issue, we have examined the assembly of the IgH locus in Pax5-deficient pro-B cells and find, unexpectedly, that 3' IgH V gene segments, which lie closest to the D-J-Cmu region, recombine efficiently, but progressively more distal V gene segments recombine progressively less efficiently. Histone acetylation and germ-line transcription correlate strongly with an open or an accessible chromatin structure thought to be permissive for V(D)J recombination, and defects in recombination are typically accompanied by deficits in these processes. We were therefore surprised to observe that distal V(H) gene segments in Pax5-/- pro-B cells exhibit no defect in these measures of accessibility. The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination.

MeSH Terms
Acetylation Alleles Animals B-Lymphocytes/metabolism Chromatin/ultrastructure DNA Nucleotidyltransferases/metabolism DNA-Binding Proteins/physiology Gene Rearrangement, B-Lymphocyte, Heavy Chain/physiology Genes, Immunoglobulin Genes, RAG-1 Histones/metabolism Homeodomain Proteins/physiology Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region/genetics Mice Mice, Inbred C57BL Mice, Knockout PAX5 Transcription Factor Transcription Factors/physiology Transcription, Genetic VDJ Recombinases
Chemicals
Chromatin DNA-Binding Proteins Histones Homeodomain Proteins Immunoglobulin Heavy Chains Immunoglobulin Variable Region PAX5 Transcription Factor Pax5 protein, mouse Transcription Factors RAG-1 protein DNA Nucleotidyltransferases VDJ Recombinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hesslein David G T
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Pflugh David L
Chowdhury Dipanjan
Bothwell Alfred L M
Sen Ranjan
Schatz David G
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1031403
Published
2003-01-01
Pages
37-42
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC195966
Subset
IM
Grants
NIAID NIH HHS · T32 AI007019 · United States
NIAID NIH HHS · AI51480 · United States
NIGMS NIH HHS · R01 GM040924 · United States
NIAID NIH HHS · R01 AI032524 · United States
NIAID NIH HHS · AI32524 · United States
NIGMS NIH HHS · GM38925 · United States
NIGMS NIH HHS · GM40924 · United States
NIAID NIH HHS · R37 AI032524 · United States
NIAID NIH HHS · AI07019 · United States
NIGMS NIH HHS · R01 GM038925 · United States
External Links
PubMed source DOI: 10.1101/gad.1031403 PMC Full Text View journal details
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