Differential regulation of histone acetylation and generation of mutations in switch regions is associated with Ig class switching

Ziqiang Li, Zhonghui Luo, Matthew D. Scharff

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Class switch recombination (CSR) allows B cells to make effective protective antibodies. CSR involves the replacement of the μ constant region with one of the downstream constant regions by recombination between the donor and recipient switch (S) regions. Although histone H3 hyperacetylation in recipient S regions was recently reported to coincide with CSR, the relative histone H3 and H4 acetylation status of the donor and recipient S regions and the relationship between the generation of mutations and histone hyperacetylation in S regions have not been addressed. Here we report that histone H3 and H4 were constitutively hyperacetylated in the donor Sμ region before and after different mitogen and cytokine treatments. We observed an increased frequency of mutations in hyperacetylated Sγ DNA segments immunoprecipitated with anti-acetyl histone antibodies. Furthermore, time course experiments revealed that the pattern of association of RNA polymerase II with S regions was much like that of H3 hyperacetylation but not always like that of H4 hyperacetylation. Collectively, our data suggest that H3 and H4 histone hyperacetylation in different S regions is regulated differently, that RNA polymerase II distribution and H3 hyperacetylation reflect the transcriptional activity of a given S region, and that transcription, hyperacetylation, and mutation are not sufficient to guarantee CSR. These findings support the notion that there are additional modifications and/or factors involved in the complex process of CSR.

Original languageEnglish (US)
Pages (from-to)15428-15433
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number43
DOIs
StatePublished - Oct 26 2004

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Immunoglobulin Class Switching
Acetylation
Histones
Mutation
Genetic Recombination
RNA Polymerase II
Antibodies
Mutation Rate
Mitogens
B-Lymphocytes
Cytokines

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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abstract = "Class switch recombination (CSR) allows B cells to make effective protective antibodies. CSR involves the replacement of the μ constant region with one of the downstream constant regions by recombination between the donor and recipient switch (S) regions. Although histone H3 hyperacetylation in recipient S regions was recently reported to coincide with CSR, the relative histone H3 and H4 acetylation status of the donor and recipient S regions and the relationship between the generation of mutations and histone hyperacetylation in S regions have not been addressed. Here we report that histone H3 and H4 were constitutively hyperacetylated in the donor Sμ region before and after different mitogen and cytokine treatments. We observed an increased frequency of mutations in hyperacetylated Sγ DNA segments immunoprecipitated with anti-acetyl histone antibodies. Furthermore, time course experiments revealed that the pattern of association of RNA polymerase II with S regions was much like that of H3 hyperacetylation but not always like that of H4 hyperacetylation. Collectively, our data suggest that H3 and H4 histone hyperacetylation in different S regions is regulated differently, that RNA polymerase II distribution and H3 hyperacetylation reflect the transcriptional activity of a given S region, and that transcription, hyperacetylation, and mutation are not sufficient to guarantee CSR. These findings support the notion that there are additional modifications and/or factors involved in the complex process of CSR.",
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