TY - JOUR
T1 - Differential regulation of histone acetylation and generation of mutations in switch regions is associated with Ig class switching
AU - Li, Ziqiang
AU - Luo, Zhonghui
AU - Scharff, Matthew D.
PY - 2004/10/26
Y1 - 2004/10/26
N2 - 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.
AB - 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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U2 - 10.1073/pnas.0406827101
DO - 10.1073/pnas.0406827101
M3 - Article
C2 - 15486086
AN - SCOPUS:7444234734
SN - 0027-8424
VL - 101
SP - 15428
EP - 15433
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 43
ER -